Trial Outcomes & Findings for Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma (NCT NCT00689936)

Last Updated: 2019-11-20

Results Overview

PFS was calculated as the time from randomization to the first documented PD or death due to any cause during the study, which ever occurred first based on the International Myeloma Working Group Uniform Response criteria (IMWG). Those who withdrew for any reason or received another anti-myeloma therapy without documented PD were censored on the date of their last response assessment, prior to receiving any other anti-myeloma therapy. Censoring rules for PFS: - No baseline assessments and no progression or death documented within the 2 scheduled assessments; Death within the lst two assessments without any adequate response assessment; Progression documented between scheduled assessments; Death between adequate assessments; no progression; study discontinuations for reasons other than PD or death; new anti-myeloma started prior to PD; death or PD after an extended lost to follow-up time period (2 or more missed scheduled assessment's).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1623 participants

Primary outcome timeframe

From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 17.7 months

Results posted on

2019-11-20

Participant Flow

This study was conducted in the Europe, Asia, North America and Pacific regions. Participants were randomized at 246 sites (165 in Europe, 23 in Asia, 39 in North America, and 19 in the Pacific). The study was co-sponsored by Intergroupe Francophone du Myélome (IFM) (for sites in France, Switzerland, and Belgium) and Celgene Corporation.

Participants were stratified at randomization by 1) age (≤ 75 versus \> 75 years), 2) stage (International Staging System Stages I or II versus Stage III), and 3) country.

Participant milestones

Participant milestones
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Active Treatment Phase STARTED	535	541	547
Active Treatment Phase Safety Population	532	540	541
Active Treatment Phase Untreated	3	1	6
Active Treatment Phase COMPLETED	0	0	0
Active Treatment Phase NOT COMPLETED	535	541	547
Progression Free Survival-PFS-Follow-Up STARTED	87	300	273
Progression Free Survival-PFS-Follow-Up COMPLETED	87	300	273
Progression Free Survival-PFS-Follow-Up NOT COMPLETED	0	0	0
Long-Term Follow Up Phase STARTED	382	463	459
Long-Term Follow Up Phase COMPLETED	255	275	315
Long-Term Follow Up Phase NOT COMPLETED	127	188	144

Reasons for withdrawal

Reasons for withdrawal
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Active Treatment Phase Adverse Event	68	71	76
Active Treatment Phase Disease Progression	273	362	339
Active Treatment Phase Withdrawal by Subject	16	16	21
Active Treatment Phase Death	60	28	37
Active Treatment Phase Lost to Follow-up	0	2	2
Active Treatment Phase Protocol Violation	2	2	4
Active Treatment Phase Study Close Out	64	26	21
Active Treatment Phase Miscellaneous	52	34	47
Long-Term Follow Up Phase Continue in Long Term Follow Up	127	188	144

Baseline Characteristics

Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=535 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=541 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=547 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.	Total n=1623 Participants Total of all reporting groups
Age, Continuous	73.2 years STANDARD_DEVIATION 6.57 • n=5 Participants	72.9 years STANDARD_DEVIATION 6.50 • n=7 Participants	73.1 years STANDARD_DEVIATION 6.32 • n=5 Participants	73.1 years STANDARD_DEVIATION 6.46 • n=4 Participants
Sex: Female, Male Female	241 Participants n=5 Participants	268 Participants n=7 Participants	260 Participants n=5 Participants	769 Participants n=4 Participants
Sex: Female, Male Male	294 Participants n=5 Participants	273 Participants n=7 Participants	287 Participants n=5 Participants	854 Participants n=4 Participants
Race/Ethnicity, Customized Asian	40 Participants n=5 Participants	43 Participants n=7 Participants	44 Participants n=5 Participants	127 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	9 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	20 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islanders	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized White or Caucasian	474 Participants n=5 Participants	480 Participants n=7 Participants	491 Participants n=5 Participants	1445 Participants n=4 Participants
Race/Ethnicity, Customized Other, Miscellaneous	6 Participants n=5 Participants	11 Participants n=7 Participants	3 Participants n=5 Participants	20 Participants n=4 Participants
Race/Ethnicity, Customized Undisclosed	5 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	11 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	37 Participants n=5 Participants	33 Participants n=7 Participants	36 Participants n=5 Participants	106 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	493 Participants n=5 Participants	505 Participants n=7 Participants	508 Participants n=5 Participants	1506 Participants n=4 Participants
International Staging System (ISS) Stage I	106 Participants n=5 Participants	106 Participants n=7 Participants	103 Participants n=5 Participants	315 Participants n=4 Participants
International Staging System (ISS) Stage II	227 Participants n=5 Participants	229 Participants n=7 Participants	225 Participants n=5 Participants	681 Participants n=4 Participants
International Staging System (ISS) Stage III	202 Participants n=5 Participants	206 Participants n=7 Participants	219 Participants n=5 Participants	627 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (fully active)	155 Participants n=5 Participants	163 Participants n=7 Participants	156 Participants n=5 Participants	474 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (restrictive but ambulatory)	257 Participants n=5 Participants	263 Participants n=7 Participants	275 Participants n=5 Participants	795 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 (ambulatory but unable to work)	119 Participants n=5 Participants	113 Participants n=7 Participants	111 Participants n=5 Participants	343 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 3-4 (limited self-care, completely disabled)	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Missing	2 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Creatinine clearance >=60 ml/min	269 Participants n=5 Participants	280 Participants n=7 Participants	285 Participants n=5 Participants	834 Participants n=4 Participants
Creatinine clearance <60 ml/min	266 Participants n=5 Participants	261 Participants n=7 Participants	261 Participants n=5 Participants	788 Participants n=4 Participants
Creatinine clearance Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Beta2 Microglobulin >5.5 mg/L	224 Participants n=5 Participants	224 Participants n=7 Participants	234 Participants n=5 Participants	682 Participants n=4 Participants
Beta2 Microglobulin <=5.5 mg/L	309 Participants n=5 Participants	316 Participants n=7 Participants	312 Participants n=5 Participants	937 Participants n=4 Participants
Beta2 Microglobulin Missing	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Albumin <=35 g/L	192 Participants n=5 Participants	209 Participants n=7 Participants	223 Participants n=5 Participants	624 Participants n=4 Participants
Albumin > 35 g/L	343 Participants n=5 Participants	331 Participants n=7 Participants	324 Participants n=5 Participants	998 Participants n=4 Participants
Albumin Missing	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Lactic Dehydrogenase <200 U/L	448 Participants n=5 Participants	442 Participants n=7 Participants	434 Participants n=5 Participants	1324 Participants n=4 Participants
Lactic Dehydrogenase >=200 U/L	86 Participants n=5 Participants	99 Participants n=7 Participants	112 Participants n=5 Participants	297 Participants n=4 Participants
Lactic Dehydrogenase Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Multiple Myeloma Subtype Immunoglobulin A	138 Participants n=5 Participants	142 Participants n=7 Participants	123 Participants n=5 Participants	403 Participants n=4 Participants
Multiple Myeloma Subtype Immunoglobulin A and Immunoglobulin G	7 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	21 Participants n=4 Participants
Multiple Myeloma Subtype Immunoglobulin A and Immunoglobulin M	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Multiple Myeloma Subtype Immunoglobulin D	4 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	15 Participants n=4 Participants
Multiple Myeloma Subtype Immunoglobulin G	334 Participants n=5 Participants	331 Participants n=7 Participants	350 Participants n=5 Participants	1015 Participants n=4 Participants
Multiple Myeloma Subtype Immunoglobulin M	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Multiple Myeloma Subtype Not available (includes light-chain disease)	49 Participants n=5 Participants	54 Participants n=7 Participants	60 Participants n=5 Participants	163 Participants n=4 Participants
Cytogenetic Risk Adverse Risk	170 Participants n=5 Participants	185 Participants n=7 Participants	189 Participants n=5 Participants	544 Participants n=4 Participants
Cytogenetic Risk Favorable Hyperdiploidy	112 Participants n=5 Participants	103 Participants n=7 Participants	102 Participants n=5 Participants	317 Participants n=4 Participants
Cytogenetic Risk Normal	148 Participants n=5 Participants	131 Participants n=7 Participants	141 Participants n=5 Participants	420 Participants n=4 Participants
Cytogenetic Risk Uncertain Risk	38 Participants n=5 Participants	56 Participants n=7 Participants	40 Participants n=5 Participants	134 Participants n=4 Participants
Cytogenetic Risk Not evaluable	34 Participants n=5 Participants	35 Participants n=7 Participants	44 Participants n=5 Participants	113 Participants n=4 Participants
Cytogenetic Risk Missing	33 Participants n=5 Participants	31 Participants n=7 Participants	31 Participants n=5 Participants	95 Participants n=4 Participants

PRIMARY outcome

Timeframe: From date of randomization until the data cut-off date of 24 May 2013. Median follow-up time for all participants was 17.1 months.

Population: The intent to treat (ITT) population included all participants who were randomized, independent of whether they received study treatment or not.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=535 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=541 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=547 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Kaplan-Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Independent Review Adjudication Committee (IRAC)	25.5 months Interval 20.7 to 29.4	20.7 months Interval 19.4 to 22.0	21.2 months Interval 19.3 to 23.2

PRIMARY outcome

Timeframe: From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 17.7 months

Population: The intent to treat population included all participants who were randomized, independent of whether they received study treatment or not.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=535 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=541 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=547 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Kaplan-Meier Estimates of PFS Based on the Response Assessment by the Investigator At the Time of Final Analysis	26.0 months Interval 20.7 to 29.7	21.0 months Interval 19.7 to 22.4	21.9 months Interval 19.8 to 23.9

SECONDARY outcome

Timeframe: From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 48.3 months

Population: ITT population included all participants who were randomized, independent of whether they received study treatment or not.

Overall survival was defined as the time between randomization and death. Participants, who died, regardless of the cause of death, were considered to have had an event. All participants who were lost to follow-up prior to the end of the trial or who were withdrawn from the trial were censored at the time of last contact. Participants who were still being treated were censored at the last available date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=535 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=541 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=547 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Kaplan Meier Estimates of Overall Survival at the Time of Final Analysis (OS)	59.1 months Interval 53.9 to 65.9	62.3 months Interval 53.6 to 68.7	49.1 months Interval 44.3 to 53.5

SECONDARY outcome

Timeframe: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm

Population: ITT population includes all participants who were randomized, independent of whether they received study treatment or not.

Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined as: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level \<100 mg/24 hours; A PR is: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to \<200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=535 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=541 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=547 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Percentage of Participants With an Objective Response Based on IRAC Review	75.1 percentage of participants	73.4 percentage of participants	62.3 percentage of participants

SECONDARY outcome

Timeframe: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm

Population: ITT population includes all participants who were randomized, independent of whether they received study treatment or not.

Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined s: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level \<100 mg/24 hours; A PR is: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to \<200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=535 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=541 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=547 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Percentage of Participants With an Objective Response Based on Investigator Assessment at Time of Final Analysis	80.7 percentage of participants	78.6 percentage of participants	67.5 percentage of participants

SECONDARY outcome

Timeframe: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median follow-up for responders was 20.1 months

Population: Study participants with at least a PR

Duration of response was defined as the duration from the time when the response criteria were first met for CR or VGPR or PR based on IMWG criteria until the first date the response criteria were met for progressive disease or until the participant died from any cause, whichever occurred first.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=402 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=397 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=341 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Kaplan Meier Estimates of Duration of Myeloma Response as Determined by the IRAC	35.0 months Interval 27.9 to 43.4	22.1 months Interval 20.3 to 24.0	22.3 months Interval 20.2 to 24.9

SECONDARY outcome

Timeframe: Disease response was assessed every 28 days until end of treatment; data cut-off date of 21 January 2016; median follow-up for responders was 19.9 months

Population: Study participants with at least a PR

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=432 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=425 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=369 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Kaplan Meier Estimates of Duration of Myeloma Response as Determined by an Investigator Assessment at Time of Final Analysis	31.5 months Interval 26.2 to 37.3	21.5 months Interval 19.2 to 23.0	22.1 months Interval 20.3 to 24.5

SECONDARY outcome

Population: Participants who had at least a PR.

The time to first myeloma response was defined as the time from randomization to the time when the response criteria for at least a PR was first met based on the IMWG criteria.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=402 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=397 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=341 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Time to First Response Based on the Review by the IRAC	1.8 months Interval 0.7 to 22.2	1.8 months Interval 0.8 to 17.1	2.8 months Interval 1.3 to 49.7

SECONDARY outcome

Population: Participants who had at least a PR.

The time to first myeloma response was defined as the time from randomization to the time when the response criteria for at least a PR was first met based on the IMWG criteria assessed by the investigator.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=430 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=425 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=368 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Time to First Response Based on the Investigator Assessment at the Time of Final Analysis	1.8 months Interval 0.5 to 22.2	1.8 months Interval 0.8 to 34.8	2.8 months Interval 1.2 to 56.3

SECONDARY outcome

Timeframe: From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 16.1 months.

Population: ITT population includes participants who were randomized, independent of whether they received study treatment or not

TTF is defined as the time between the randomization and discontinuation of study treatment for any reason, including disease progression (determined by IRAC based on the IMWG response criteria), treatment toxicity, start of another anti-myeloma therapy (AMT) or death.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=535 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=541 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=547 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Kaplan Meier Estimates of Time to Treatment Failure (TTF)	16.9 months Interval 14.1 to 18.4	17.2 months Interval 14.6 to 18.2	14.1 months Interval 12.0 to 16.1

SECONDARY outcome

Timeframe: From date of randomization until the data cut-off date of 21 January 2016; median follow up for all participants was 16.1 months.

Population: ITT population includes participants who were randomized, independent of whether they received study treatment or not

TTF is defined as the time between the randomization and discontinuation of study treatment for any reason, including disease progression (determined by the investigators assessment based on the IMWG response criteria), treatment toxicity, start of another anti-myeloma therapy (AMT) or death.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=535 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=541 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=547 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Kaplan Meier Estimates of Time to Treatment Failure (TTF) at the Time of Final Analysis	16.9 months Interval 14.1 to 18.4	17.2 months Interval 14.6 to 18.2	14.1 months Interval 12.0 to 16.1

SECONDARY outcome

Timeframe: From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 23.0 months

Population: ITT population includes all participants who were randomized, independent of whether they received study treatment or not

Time to second-line anti-myeloma therapy was defined as time from randomization to the start of another non-protocol anti-myeloma therapy.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=535 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=541 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=547 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Kaplan Meier Estimates for Time to Second-line Anti-myeloma Treatment (AMT)	39.1 months Interval 32.8 to Could not be estimated due to the low number of events at the time of analysis	28.5 months Interval 26.9 to 30.4	26.7 months Interval 24.0 to 29.9

SECONDARY outcome

Timeframe: From date of randomization until the data cut-off of date 21 January 2016; median follow-up for all participants was 23.0 months

Population: ITT population includes all participants who were randomized, independent of whether they received study treatment or not.

Time to second-line anti-myeloma therapy is defined as time from randomization to the start of another non-protocol anti-myeloma therapy. Those who do not receive another anti-myeloma therapy were censored at the last assessment or follow-up visit known to have received no new therapy.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=535 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=541 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=547 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Kaplan Meier Estimates of Time to Second Line Therapy AMT at the Time of Final Analysis	36.7 months Interval 31.9 to 45.2	28.5 months Interval 26.9 to 30.4	26.7 months Interval 24.0 to 29.1

SECONDARY outcome

Timeframe: Disease response was assessed every 28 days until end of treatment; data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm

Population: ITT population; Participants with second line AMT.

Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined s: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level \<100 mg/24 hours; A PR is: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to \<200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=299 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=377 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=381 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Percentage of Participants With an Objective Response After Second-line Anti-myeloma Treatment at the Time of Final Analysis	46.2 percentage of participants	53.1 percentage of participants	45.7 percentage of participants

SECONDARY outcome

Population: ITT population with Cytogenetic risk of Adverse Risk

Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level \<100 mg/24 hours; A PR is ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to \<200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=170 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=185 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=189 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Percentage of Participants With a Myeloma Response by Adverse Risk Cytogenetic Risk Category Based on IRAC Review.	70.0 Percentage of participants	69.7 Percentage of participants	58.2 Percentage of participants

SECONDARY outcome

Population: ITT population with a Cytogenetic Risk of Favorable Hyperploidy

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=112 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=103 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=102 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Percentage of Participants With a Myeloma Response by Favorable Hyperdiploidy Risk Cytogenetic Risk Category Based on IRAC Review	80.4 percentage of participants	81.6 percentage of participants	70.6 percentage of participants

SECONDARY outcome

Population: ITT population with a cytogenetic risk of normal

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=148 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=131 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=141 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Percentage of Participants With a Myeloma Response by Normal Risk Cytogenetic Risk Category Based on IRAC Review	80.4 percentage of particpants	74.8 percentage of particpants	61.0 percentage of particpants

SECONDARY outcome

Population: ITT population with a Cytogenetic Risk of Uncertain Risk

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=38 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=56 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=40 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Percentage of Participants With a Myeloma Response by Uncertain Risk Cytogenetic Risk Category Based on IRAC Review	60.5 percentage of participants	76.8 percentage of participants	57.5 percentage of participants

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: Intent to Treat (ITT) population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in QOL or functioning and positive values indicate improvement.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=508 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=507 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=508 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain Month 1	0.4 units on a scale Standard Deviation 23.98	-1.3 units on a scale Standard Deviation 23.93	1.0 units on a scale Standard Deviation 23.68
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain Month 3	4.8 units on a scale Standard Deviation 24.15	4.7 units on a scale Standard Deviation 25.15	4.3 units on a scale Standard Deviation 26.04
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain Month 6	5.9 units on a scale Standard Deviation 25.93	5.4 units on a scale Standard Deviation 23.88	6.1 units on a scale Standard Deviation 25.98
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain Month 12	4.8 units on a scale Standard Deviation 26.42	3.2 units on a scale Standard Deviation 25.38	6.5 units on a scale Standard Deviation 25.90
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain Month 18	6.4 units on a scale Standard Deviation 28.02	5.7 units on a scale Standard Deviation 24.86	4.8 units on a scale Standard Deviation 27.05
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain Study discontinuation	-0.1 units on a scale Standard Deviation 27.07	5.0 units on a scale Standard Deviation 27.33	0.3 units on a scale Standard Deviation 28.07

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: Intent to Treat (ITT) population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=511 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=514 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=509 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain Month 1	-1.7 units on a scale Standard Deviation 21.11	-1.4 units on a scale Standard Deviation 19.56	-0.9 units on a scale Standard Deviation 21.28
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain Month 3	3.4 units on a scale Standard Deviation 23.33	4.7 units on a scale Standard Deviation 22.94	2.2 units on a scale Standard Deviation 23.68
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain Month 6	4.7 units on a scale Standard Deviation 25.09	7.6 units on a scale Standard Deviation 22.85	5.3 units on a scale Standard Deviation 24.52
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain Month 12	5.0 units on a scale Standard Deviation 25.65	7.4 units on a scale Standard Deviation 23.40	6.9 units on a scale Standard Deviation 27.22
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain Month 18	6.9 units on a scale Standard Deviation 26.71	6.8 units on a scale Standard Deviation 23.58	8.3 units on a scale Standard Deviation 27.10
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain Discontinuation Visit	-0.1 units on a scale Standard Deviation 29.70	3.0 units on a scale Standard Deviation 27.32	-0.1 units on a scale Standard Deviation 27.58

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: Intent to Treat (ITT) population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=509 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=508 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=508 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain Month 1	-2.7 units on a scale Standard Deviation 29.94	-4.6 units on a scale Standard Deviation 28.20	-2.4 units on a scale Standard Deviation 30.48
Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain Month 3	2.4 units on a scale Standard Deviation 33.32	6.3 units on a scale Standard Deviation 32.43	4.1 units on a scale Standard Deviation 34.23
Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain Month 6	6.3 units on a scale Standard Deviation 35.44	8.6 units on a scale Standard Deviation 32.42	8.2 units on a scale Standard Deviation 36.09
Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain Month 12	7.8 units on a scale Standard Deviation 36.60	9.4 units on a scale Standard Deviation 34.15	11.8 units on a scale Standard Deviation 38.94
Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain Month 18	8.0 units on a scale Standard Deviation 35.34	9.1 units on a scale Standard Deviation 34.35	14.5 units on a scale Standard Deviation 39.03
Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain Discontinuation Visit	-0.3 units on a scale Standard Deviation 39.58	3.8 units on a scale Standard Deviation 36.34	-1.0 units on a scale Standard Deviation 38.41

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: Intent to Treat (ITT) population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=509 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=510 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=510 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain Month 1	0.6 units on a scale Standard Deviation 22.13	0.1 units on a scale Standard Deviation 20.73	1.0 units on a scale Standard Deviation 21.52
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain Month 3	3.8 units on a scale Standard Deviation 22.29	3.9 units on a scale Standard Deviation 22.11	2.1 units on a scale Standard Deviation 22.27
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain Month 6	4.6 units on a scale Standard Deviation 24.36	5.8 units on a scale Standard Deviation 22.39	5.5 units on a scale Standard Deviation 22.55
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain Month 12	4.6 units on a scale Standard Deviation 24.08	4.9 units on a scale Standard Deviation 22.23	5.1 units on a scale Standard Deviation 22.37
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain Month 18	5.8 units on a scale Standard Deviation 25.61	3.1 units on a scale Standard Deviation 23.31	5.1 units on a scale Standard Deviation 22.99
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain Discontinuation Visit	2.6 units on a scale Standard Deviation 24.30	3.7 units on a scale Standard Deviation 23.77	-0.0 units on a scale Standard Deviation 24.72

SECONDARY outcome

Timeframe: Cycle 1 Day 1, (Baseline) then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: Intent to Treat (ITT) population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=509 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=510 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=510 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain Month 1	-1.2 units on a scale Standard Deviation 21.73	-1.7 units on a scale Standard Deviation 19.08	-1.8 units on a scale Standard Deviation 24.07
Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain Month 3	-0.7 units on a scale Standard Deviation 22.89	1.8 units on a scale Standard Deviation 20.94	-1.5 units on a scale Standard Deviation 24.02
Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain Month 6	-0.9 units on a scale Standard Deviation 22.57	0.9 units on a scale Standard Deviation 19.77	-0.3 units on a scale Standard Deviation 23.55
Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain Month 12	-1.6 units on a scale Standard Deviation 25.05	-1.2 units on a scale Standard Deviation 20.19	-0.6 units on a scale Standard Deviation 22.97
Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain Month 18	-2.2 units on a scale Standard Deviation 25.61	-2.8 units on a scale Standard Deviation 20.97	-0.7 units on a scale Standard Deviation 23.99
Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain Discontinuation Visit	-4.9 units on a scale Standard Deviation 27.57	-2.6 units on a scale Standard Deviation 22.34	-7.1 units on a scale Standard Deviation 25.15

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: Intent to Treat (ITT) population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=505 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=503 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=503 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain Month 18	4.2 units on a scale Standard Deviation 34.99	3.2 units on a scale Standard Deviation 31.67	6.0 units on a scale Standard Deviation 35.20
Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain Month 1	-4.3 units on a scale Standard Deviation 29.10	-2.2 units on a scale Standard Deviation 27.44	-1.4 units on a scale Standard Deviation 30.52
Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain Month 3	0.7 units on a scale Standard Deviation 29.36	2.0 units on a scale Standard Deviation 30.93	2.4 units on a scale Standard Deviation 30.70
Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain Month 6	4.0 units on a scale Standard Deviation 32.48	5.2 units on a scale Standard Deviation 28.50	3.4 units on a scale Standard Deviation 35.24
Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain Month 12	2.9 units on a scale Standard Deviation 34.96	3.8 units on a scale Standard Deviation 32.29	5.8 units on a scale Standard Deviation 33.68
Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain Discontinuation Visit	-1.2 units on a scale Standard Deviation 33.50	2.7 units on a scale Standard Deviation 33.37	-3.5 units on a scale Standard Deviation 33.20

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation

Population: Intent to Treat (ITT) population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=511 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=514 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=512 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain Month 1	2.6 units on a scale Standard Deviation 25.32	4.4 units on a scale Standard Deviation 24.03	2.8 units on a scale Standard Deviation 25.44
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain Month 3	-2.5 units on a scale Standard Deviation 28.15	-3.4 units on a scale Standard Deviation 25.16	-1.8 units on a scale Standard Deviation 28.53
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain Month 6	-3.7 units on a scale Standard Deviation 28.54	-5.9 units on a scale Standard Deviation 26.37	-4.5 units on a scale Standard Deviation 29.09
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain Month 12	-4.3 units on a scale Standard Deviation 29.47	-2.3 units on a scale Standard Deviation 26.63	-3.9 units on a scale Standard Deviation 29.56
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain Month 18	-3.1 units on a scale Standard Deviation 29.82	0.1 units on a scale Standard Deviation 29.12	-4.3 units on a scale Standard Deviation 30.05
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain Discontinuation Visit	0.3 units on a scale Standard Deviation 29.75	-1.6 units on a scale Standard Deviation 29.11	2.7 units on a scale Standard Deviation 30.15

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: Intent to Treat (ITT) population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=511 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=514 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=512 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Pain Domain Month 1	-5.4 units on a scale Standard Deviation 31.89	-4.4 units on a scale Standard Deviation 30.70	-7.8 units on a scale Standard Deviation 30.93
Change From Baseline in the EORTC QLQ-C30 Pain Domain Month 3	-13.4 units on a scale Standard Deviation 34.28	-13.1 units on a scale Standard Deviation 32.32	-12.1 units on a scale Standard Deviation 31.98
Change From Baseline in the EORTC QLQ-C30 Pain Domain Month 6	-14.4 units on a scale Standard Deviation 35.64	-16.1 units on a scale Standard Deviation 33.44	-13.4 units on a scale Standard Deviation 34.45
Change From Baseline in the EORTC QLQ-C30 Pain Domain Month 12	-14.0 units on a scale Standard Deviation 36.05	-14.7 units on a scale Standard Deviation 32.34	-14.3 units on a scale Standard Deviation 32.85
Change From Baseline in the EORTC QLQ-C30 Pain Domain Month 18	-14.4 units on a scale Standard Deviation 35.03	-12.4 units on a scale Standard Deviation 35.28	-14.7 units on a scale Standard Deviation 32.81
Change From Baseline in the EORTC QLQ-C30 Pain Domain Discontinuation Visit	-8.0 units on a scale Standard Deviation 39.37	-7.9 units on a scale Standard Deviation 37.65	-6.0 units on a scale Standard Deviation 37.09

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: Intent to Treat (ITT) population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea/Vomiting Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=511 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=513 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=512 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain Month 1	1.8 units on a scale Standard Deviation 20.05	-0.5 units on a scale Standard Deviation 23.19	4.0 units on a scale Standard Deviation 22.91
Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain Month 3	-1.1 units on a scale Standard Deviation 19.42	-2.5 units on a scale Standard Deviation 21.92	-1.2 units on a scale Standard Deviation 19.89
Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain Month 6	-1.3 units on a scale Standard Deviation 18.53	-4.0 units on a scale Standard Deviation 21.52	-3.9 units on a scale Standard Deviation 19.57
Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain Month 18	-2.3 units on a scale Standard Deviation 19.20	-2.7 units on a scale Standard Deviation 18.92	-3.9 units on a scale Standard Deviation 19.44
Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain Discontinuation Visit	0.4 units on a scale Standard Deviation 21.43	-4.2 units on a scale Standard Deviation 24.37	1.0 units on a scale Standard Deviation 21.46
Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain Month 12	-2.2 units on a scale Standard Deviation 17.16	-3.6 units on a scale Standard Deviation 18.86	-3.9 units on a scale Standard Deviation 19.09

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: ITT population includes all participants with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=509 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=508 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=506 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain Month 3	-0.8 units on a scale Standard Deviation 31.87	-1.9 units on a scale Standard Deviation 29.45	2.0 units on a scale Standard Deviation 32.49
Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain Month 6	-2.3 units on a scale Standard Deviation 33.12	-2.9 units on a scale Standard Deviation 29.66	0.1 units on a scale Standard Deviation 30.29
Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain Month 12	-3.5 units on a scale Standard Deviation 30.97	-1.6 units on a scale Standard Deviation 29.23	-1.6 units on a scale Standard Deviation 32.76
Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain Month 18	-1.8 units on a scale Standard Deviation 32.73	2.9 units on a scale Standard Deviation 28.33	0.4 units on a scale Standard Deviation 32.68
Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain Discontinuation Visit	-1.0 units on a scale Standard Deviation 37.42	0.8 units on a scale Standard Deviation 31.01	7.8 units on a scale Standard Deviation 33.72
Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain Month 1	0.9 units on a scale Standard Deviation 30.87	3.6 units on a scale Standard Deviation 29.85	4.2 units on a scale Standard Deviation 32.04

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: Intent to Treat (ITT) population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Insomnia Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=510 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=513 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=511 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Insomnia Domain Month 12	-1.0 units on a scale Standard Deviation 34.78	1.1 units on a scale Standard Deviation 32.47	-9.6 units on a scale Standard Deviation 31.00
Change From Baseline in the EORTC QLQ-C30 Insomnia Domain Month 18	-0.5 units on a scale Standard Deviation 37.11	1.4 units on a scale Standard Deviation 35.72	-6.0 units on a scale Standard Deviation 34.42
Change From Baseline in the EORTC QLQ-C30 Insomnia Domain Discontinuation Visit	-5.2 units on a scale Standard Deviation 36.47	-1.6 units on a scale Standard Deviation 31.27	-4.5 units on a scale Standard Deviation 36.98
Change From Baseline in the EORTC QLQ-C30 Insomnia Domain Month 1	2.1 units on a scale Standard Deviation 33.34	3.2 units on a scale Standard Deviation 34.32	-10.5 units on a scale Standard Deviation 30.47
Change From Baseline in the EORTC QLQ-C30 Insomnia Domain Month 3	0.2 units on a scale Standard Deviation 35.11	-1.3 units on a scale Standard Deviation 33.54	-8.9 units on a scale Standard Deviation 35.28
Change From Baseline in the EORTC QLQ-C30 Insomnia Domain Month 6	-1.2 units on a scale Standard Deviation 34.84	-1.9 units on a scale Standard Deviation 31.43	-11.6 units on a scale Standard Deviation 32.96

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: ITT population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Scale is scored between 0 and 100, with a high score indicating a higher level of appetite loss. Negative change from Baseline values indicate improvement in appetite and positive values indicate worsening of appetite.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=509 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=512 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=510 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain Month 1	1.3 units on a scale Standard Deviation 33.46	2.9 units on a scale Standard Deviation 31.87	1.0 units on a scale Standard Deviation 32.35
Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain Month 3	-5.9 units on a scale Standard Deviation 38.34	-3.3 units on a scale Standard Deviation 35.25	-6.2 units on a scale Standard Deviation 35.03
Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain Discontinuation Visit	-1.0 units on a scale Standard Deviation 36.77	-7.5 units on a scale Standard Deviation 37.49	-2.6 units on a scale Standard Deviation 37.18
Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain Month 6	-9.8 units on a scale Standard Deviation 40.02	-8.6 units on a scale Standard Deviation 33.98	-13.5 units on a scale Standard Deviation 35.98
Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain Month 12	-7.3 units on a scale Standard Deviation 37.07	-6.4 units on a scale Standard Deviation 35.30	-10.5 units on a scale Standard Deviation 34.16
Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain Month 18	-8.1 units on a scale Standard Deviation 35.97	-5.1 units on a scale Standard Deviation 33.29	-12.2 units on a scale Standard Deviation 31.88

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: ITT population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Scale is scored between 0 and 100, with a high score indicating a higher level of constipation. Negative change from Baseline values indicate improvement in constipation and positive values indicate worsening of constipation.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=508 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=511 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=510 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Constipation Domain Month 1	8.3 units on a scale Standard Deviation 36.74	6.3 units on a scale Standard Deviation 36.18	18.4 units on a scale Standard Deviation 41.23
Change From Baseline in the EORTC QLQ-C30 Constipation Domain Month 3	1.8 units on a scale Standard Deviation 37.53	0.0 units on a scale Standard Deviation 37.02	13.9 units on a scale Standard Deviation 39.30
Change From Baseline in the EORTC QLQ-C30 Constipation Domain Month 6	-2.4 units on a scale Standard Deviation 37.51	-5.1 units on a scale Standard Deviation 37.39	6.8 units on a scale Standard Deviation 40.41
Change From Baseline in the EORTC QLQ-C30 Constipation Domain Month 12	-2.4 units on a scale Standard Deviation 38.79	-5.2 units on a scale Standard Deviation 38.09	3.7 units on a scale Standard Deviation 38.28
Change From Baseline in the EORTC QLQ-C30 Constipation Domain Month 18	-4.5 units on a scale Standard Deviation 35.42	-5.9 units on a scale Standard Deviation 36.65	0.0 units on a scale Standard Deviation 37.06
Change From Baseline in the EORTC QLQ-C30 Constipation Domain Discontinuation Visit	-7.9 units on a scale Standard Deviation 39.98	-7.5 units on a scale Standard Deviation 39.20	-2.2 units on a scale Standard Deviation 38.86

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: ITT population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarrhea Scale is scored between 0 and 100, with a high score indicating a higher level of diarrhea. Negative change from Baseline values indicate improvement in diarrhea and positive values indicate worsening of diarrhea.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=508 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=509 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=510 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain Month 1	3.8 units on a scale Standard Deviation 25.53	2.3 units on a scale Standard Deviation 24.94	-0.6 units on a scale Standard Deviation 18.79
Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain Month 3	3.7 units on a scale Standard Deviation 24.99	3.4 units on a scale Standard Deviation 27.27	-2.4 units on a scale Standard Deviation 18.61
Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain Month 6	8.2 units on a scale Standard Deviation 28.36	6.0 units on a scale Standard Deviation 27.95	-2.2 units on a scale Standard Deviation 21.19
Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain Month 12	11.8 units on a scale Standard Deviation 31.35	9.1 units on a scale Standard Deviation 28.74	-2.5 units on a scale Standard Deviation 17.26
Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain Month 18	14.8 units on a scale Standard Deviation 31.20	10.9 units on a scale Standard Deviation 30.96	-1.7 units on a scale Standard Deviation 17.46
Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain Discontinuation Visit	10.8 units on a scale Standard Deviation 29.56	6.4 units on a scale Standard Deviation 31.38	-0.5 units on a scale Standard Deviation 19.39

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: ITT population with available data.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Difficulties Scale is scored between 0 and 100, with a high score indicating a higher level of financial difficulties. Negative change from Baseline values indicate improvement in financial difficulties and positive values indicate worsening of financial difficulties.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=501 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=504 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=502 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain Month 1	2.1 units on a scale Standard Deviation 21.43	-0.3 units on a scale Standard Deviation 20.59	0.5 units on a scale Standard Deviation 22.98
Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain Month 3	1.9 units on a scale Standard Deviation 23.09	-0.4 units on a scale Standard Deviation 21.88	1.9 units on a scale Standard Deviation 21.48
Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain Month 6	1.4 units on a scale Standard Deviation 22.92	-0.3 units on a scale Standard Deviation 21.24	0.7 units on a scale Standard Deviation 24.57
Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain Month 12	0.4 units on a scale Standard Deviation 23.99	1.6 units on a scale Standard Deviation 23.28	1.1 units on a scale Standard Deviation 23.16
Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain Month 18	2.0 units on a scale Standard Deviation 22.23	1.8 units on a scale Standard Deviation 23.30	0.4 units on a scale Standard Deviation 21.20
Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain Discontinuation Visit	1.9 units on a scale Standard Deviation 27.19	0.5 units on a scale Standard Deviation 23.84	5.0 units on a scale Standard Deviation 24.82

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: ITT population with available data.

EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; a higher score indicates more severe disease symptom(s).

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=510 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=512 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=511 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale Month 1	-4.0 units on a scale Standard Deviation 18.75	-4.1 units on a scale Standard Deviation 19.37	-4.4 units on a scale Standard Deviation 19.04
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale Month 3	-9.1 units on a scale Standard Deviation 21.66	-10.0 units on a scale Standard Deviation 19.97	-7.0 units on a scale Standard Deviation 20.43
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale Month 6	-8.8 units on a scale Standard Deviation 20.89	-9.9 units on a scale Standard Deviation 20.94	-7.9 units on a scale Standard Deviation 21.94
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale Month 12	-7.8 units on a scale Standard Deviation 21.74	-8.7 units on a scale Standard Deviation 20.29	-6.5 units on a scale Standard Deviation 21.58
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale Month 18	-8.7 units on a scale Standard Deviation 23.50	-6.2 units on a scale Standard Deviation 23.30	-7.9 units on a scale Standard Deviation 21.26
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale Discontinuation Visit	-3.5 units on a scale Standard Deviation 24.82	-4.5 units on a scale Standard Deviation 24.90	-3.7 units on a scale Standard Deviation 23.54

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: ITT population with available data.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=509 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=511 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=510 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale Month 1	2.5 units on a scale Standard Deviation 13.72	4.0 units on a scale Standard Deviation 14.89	5.6 units on a scale Standard Deviation 15.00
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale Month 3	1.0 units on a scale Standard Deviation 15.23	1.2 units on a scale Standard Deviation 14.67	3.5 units on a scale Standard Deviation 15.40
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale Month 6	1.7 units on a scale Standard Deviation 15.58	-0.4 units on a scale Standard Deviation 14.39	2.9 units on a scale Standard Deviation 17.28
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale Month 12	1.9 units on a scale Standard Deviation 14.49	1.2 units on a scale Standard Deviation 16.20	4.7 units on a scale Standard Deviation 17.17
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale Month 18	2.2 units on a scale Standard Deviation 15.63	2.3 units on a scale Standard Deviation 17.36	4.3 units on a scale Standard Deviation 16.37
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale Discontinuation Visit	0.6 units on a scale Standard Deviation 15.85	-1.0 units on a scale Standard Deviation 15.81	3.8 units on a scale Standard Deviation 16.52

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: ITT population with available data.

EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; for the future perspective scale, a higher score indicates a better perspective of the future.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=504 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=508 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=509 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale Month 1	4.7 units on a scale Standard Deviation 22.17	3.9 units on a scale Standard Deviation 20.94	3.3 units on a scale Standard Deviation 23.20
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale Month 3	8.5 units on a scale Standard Deviation 23.28	9.2 units on a scale Standard Deviation 22.95	6.3 units on a scale Standard Deviation 25.06
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale Month 6	9.8 units on a scale Standard Deviation 23.67	12.3 units on a scale Standard Deviation 24.84	8.0 units on a scale Standard Deviation 25.26
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale Month 12	10.8 units on a scale Standard Deviation 21.90	12.1 units on a scale Standard Deviation 24.41	10.0 units on a scale Standard Deviation 26.30
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale Month 18	12.7 units on a scale Standard Deviation 23.96	11.7 units on a scale Standard Deviation 24.76	9.5 units on a scale Standard Deviation 21.75
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale Discontinuation Visit	5.8 units on a scale Standard Deviation 25.91	8.8 units on a scale Standard Deviation 26.71	3.2 units on a scale Standard Deviation 27.13

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: ITT population with available data.

EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; for the body image scale, a higher score indicates a better body image.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=492 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=498 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=504 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale Month 1	-4.5 units on a scale Standard Deviation 29.44	-1.5 units on a scale Standard Deviation 27.19	-1.6 units on a scale Standard Deviation 29.97
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale Month 3	-1.7 units on a scale Standard Deviation 27.54	0.8 units on a scale Standard Deviation 26.23	-3.0 units on a scale Standard Deviation 29.38
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale Month 6	-1.4 units on a scale Standard Deviation 27.84	1.5 units on a scale Standard Deviation 29.72	-2.8 units on a scale Standard Deviation 33.07
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale Month 12	-1.4 units on a scale Standard Deviation 29.60	-0.4 units on a scale Standard Deviation 31.64	-2.6 units on a scale Standard Deviation 31.96
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale Month 18	-2.3 units on a scale Standard Deviation 28.09	-0.3 units on a scale Standard Deviation 31.04	-1.1 units on a scale Standard Deviation 33.60
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale Discontinuation Visit	-5.6 units on a scale Standard Deviation 34.29	1.8 units on a scale Standard Deviation 30.66	-5.6 units on a scale Standard Deviation 33.73

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit

Population: ITT population with available data.

EQ-5D is a self-administered questionnaire that assesses health-related quality of life. The EQ-5D descriptive health profile comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). A unique EQ-5D health state is defined by combining one level from each of the five dimensions into a single utility index score. EQ-5D index values range from -0.59 to 1.00 where higher EQ-5D scores represent better health status. A positive change from baseline score indicates improvement in health status and better health state.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=490 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=492 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=490 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score Month 1	0.0 units on a scale Standard Deviation 0.29	-0.0 units on a scale Standard Deviation 0.31	0.0 units on a scale Standard Deviation 0.28
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score Month 3	0.1 units on a scale Standard Deviation 0.33	0.1 units on a scale Standard Deviation 0.32	0.1 units on a scale Standard Deviation 0.32
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score Month 6	0.1 units on a scale Standard Deviation 0.32	0.1 units on a scale Standard Deviation 0.31	0.1 units on a scale Standard Deviation 0.34
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score Month 12	0.1 units on a scale Standard Deviation 0.33	0.1 units on a scale Standard Deviation 0.31	0.1 units on a scale Standard Deviation 0.35
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score Month 18	0.1 units on a scale Standard Deviation 0.36	0.1 units on a scale Standard Deviation 0.32	0.1 units on a scale Standard Deviation 0.35
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score Discontinuation Visit	0.0 units on a scale Standard Deviation 0.40	0.0 units on a scale Standard Deviation 0.35	0.0 units on a scale Standard Deviation 0.39

SECONDARY outcome

Timeframe: Day 1 (randomization) up to last visit completed 25 July 2016

Population: Healthcare Resource Utilization not analyzed.

HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective. The rate of inpatient hospitalizations per patient year was calculated as the total number of hospitalizations divided by the total number of patient-years followed in the study period. Patient-years (PY) were calculated as the duration from baseline to last available HRQL assessment for each patient.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug through 28 days following the discontinuation visit from active treatment phase; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm

Population: Safety population included all participants who received at least one dose treatment dose of treatment in any arm

A TEAE is any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=532 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=540 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=541 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to Thalidomide withdrawal	0 Participants	0 Participants	146 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 adverse event (AE)	529 Participants	536 Participants	539 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 grade (Gr) 3 or 4 AE	453 Participants	433 Participants	480 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 grade (Gr) 5 AE	50 Participants	36 Participants	38 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 serious adverse event (SAE)	359 Participants	308 Participants	270 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 AE related to Lenalidomide/Dex/Mel/Pred/Thal	506 Participants	501 Participants	527 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 AE related to Lenalidomide	482 Participants	481 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 AE related to dexamethasone	429 Participants	410 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 AE related to melphalan	0 Participants	0 Participants	441 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 AE related to prednisone	0 Participants	0 Participants	326 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 AE related to thalidomide	0 Participants	0 Participants	493 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE related to Lenalidomide/Dex or Mel/Pred/Thal	269 Participants	269 Participants	145 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 Gr 3 or 4 AE related to Len/Dex/Mel/Pred/Thal	373 Participants	326 Participants	423 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 grade 3 or 4 AE related to Lenalidomide	342 Participants	290 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 grade 3 or 4 AE related to dexamethasone	229 Participants	177 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 grade 3 or 4 AE related to melphalan	0 Participants	0 Participants	307 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 grade 3 or 4 AE related to prednisone	0 Participants	0 Participants	118 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 grade 3 or 4 AE related to Thalidomide	0 Participants	0 Participants	316 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1Gr 3 or 4 AE related to Len/Dex or Mel/Pred/Thal	131 Participants	104 Participants	49 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 Grade 5 AE related to Len/Dex/Mel/Pred/Thal	17 Participants	11 Participants	10 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 Grade 5 AE related to Lenalidomide	12 Participants	9 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 Grade 5 AE related to Dexamethasone	16 Participants	7 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 Grade 5 AE related to melphalan	0 Participants	0 Participants	6 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 Grade 5 AE related to prednisone	0 Participants	0 Participants	5 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥ 1 Grade 5 AE related to Thalidomide	0 Participants	0 Participants	5 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 Grade 5 AE related to Len/Dex or Mel/Pred/Thal	11 Participants	5 Participants	2 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 SAE related to Len/Dex/Mel/Pred/Thal	195 Participants	158 Participants	142 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 SAE related to Lenalidomide	165 Participants	130 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 SAE related to dexamethasone	130 Participants	97 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 SAE related to melphalan	0 Participants	0 Participants	75 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 SAE related to prednisone	0 Participants	0 Participants	62 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 SAE related to thalidomide	0 Participants	0 Participants	94 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 SAE related to Len/Dex or Mel/Pred/Thal	95 Participants	64 Participants	27 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1AE leading to Len/Dex/Mel/Pred/Thal Withdrawal	157 Participants	109 Participants	153 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to Lenalidomide withdrawal	109 Participants	93 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to dexamethasone withdrawal	152 Participants	104 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to melphalan withdrawal	0 Participants	0 Participants	83 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to prednisone withdrawal	0 Participants	0 Participants	78 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1AE leading to Len/DexOR Mel/Pred/Thal Withdrawal	96 Participants	84 Participants	71 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1AE leading to Len/Dex/Mel/Pred/Thal reduction	279 Participants	214 Participants	348 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to Lenalidomide reduction	203 Participants	155 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to dexamethasone reduction	170 Participants	118 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to melphalan reduction	0 Participants	0 Participants	199 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to prednisone reduction	0 Participants	0 Participants	47 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to thalidomide reduction	0 Participants	0 Participants	254 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1AE leading to Len/Dex or Mel/Pred/Thal reduction	30 Participants	20 Participants	2 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to Rd or MPT interruption	368 Participants	321 Participants	419 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to Lenalidomide interruption	353 Participants	301 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to dexamethasone interruption	319 Participants	280 Participants	0 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to melphalan interruption	0 Participants	0 Participants	328 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to prednisone interruption	0 Participants	0 Participants	324 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to Thalidomide interruption	0 Participants	0 Participants	388 Participants
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase ≥1 AE leading to Len and Dex or MPT interruption	290 Participants	241 Participants	249 Participants

SECONDARY outcome

Timeframe: Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm

Population: Safety Population with baseline and postbaseline CrCl data.

Renal function was assessed for participants from baseline to the most extreme value in creatinine clearance calculated using the Cockcroft-Gault estimation.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=494 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=506 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=484 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl< 30 mL/min to CrCl< 30 mL/min	15 participants	17 participants	19 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl < 30 mL/min to CrCl ≥ 30 but < 50 mL/min	18 participants	14 participants	19 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl < 30 mL/min to CrCl ≥ 50 but < 80 mL/min	7 participants	8 participants	5 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl< 30 mL/min to ≥ 80 mL/min	2 participants	2 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl≥ 30 but < 50 mL/min to < 30 mL/min	1 participants	2 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl ≥ 30 but < 50 mL/min to CrCl ≥ 30 but < 50 mL	37 participants	41 participants	41 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl ≥ 30 but < 50 mL/min to CrCl ≥ 50 but < 80 mL	67 participants	55 participants	65 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl ≥ 30 but < 50 mL/min to ≥ 80 mL/min	9 participants	12 participants	2 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl ≥ 50 but < 80 mL to CrCl< 30 mL/min	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl ≥ 50 but < 80 mL to CrCl ≥ 30 but < 50 mL/min	4 participants	1 participants	4 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl ≥ 50 but < 80 mL to CrCl ≥ 50 but < 80 mL/min	112 participants	130 participants	102 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl ≥ 50 but < 80 mL to ≥ 80 mL/min	107 participants	99 participants	97 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl ≥ 80 mL/min to CrCl< 30 mL/min	0 participants	1 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl ≥ 80 mL/min to CrCl ≥ 30 but < 50 mL/min	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl ≥ 80 mL/min to CrCl ≥ 50 but < 80 mL/min	6 participants	10 participants	9 participants
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase CrCl ≥ 80 mL/min to CrCl ≥ 80 mL/min	109 participants	114 participants	121 participants

SECONDARY outcome

Timeframe: Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm

Population: Safety Population; includes participants with baseline and postbaseline absolute neutrophil laboratory test grade information

Neutrophil counts was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=525 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=534 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=526 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Normal Baseline Grade to Normal Postbaseline Grade	103 participants	133 participants	37 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Normal Baseline Grade to Grade 1 postbaseline	96 participants	85 participants	79 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Normal Baseline Grade to Grade 2 postbaseline	121 participants	109 participants	128 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Normal Baseline Grade to Grade 3 postbaseline	70 participants	71 participants	141 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Normal Baseline Grade to Grade 4 postbaseline	21 participants	30 participants	45 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 1 Baseline to Normal postbaseline	7 participants	6 participants	2 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade1 Baseline to Grade 1 postbaseline	8 participants	11 participants	2 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 1 Baseline to Grade 2 postbaseline	17 participants	15 participants	11 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 1 Baseline to Grade 3 postbaseline	25 participants	30 participants	20 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 1 Baseline to Grade 4 postbaseline	9 participants	4 participants	21 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 2 Baseline to normal postbaseline	1 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 2 Baseline to Grade 1 postbaseline	1 participants	1 participants	1 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 2 Baseline to Grade 2 postbaseline	14 participants	11 participants	7 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 2 Baseline to Grade 3 postbaseline	18 participants	18 participants	21 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 2 Baseline to Grade 4 postbaseline	9 participants	5 participants	10 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 3 Baseline to Normal postbaseline	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 3 Baseline to Grade 1 postbaseline	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 3 Baseline to Grade 2 postbaseline	2 participants	1 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 3 Baseline to Grade 3 postbaseline	2 participants	2 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade3 Baseline to Grade 4 postbaseline	0 participants	2 participants	1 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 4 Baseline to Normal postbaseline Grade	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 4 Baseline to Grade 1 postbaseline Grade	1 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 4 Baseline to Grade 2 postbaseline	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 4 Baseline Grade to Grade 3 postbaseline	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase Grade 4 Baseline to Grade 4 postbaseline	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm

Population: Safety Population; Includes participants with baseline and postbaseline hemoglobin laboratory test grade information

Hemoglobin was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=527 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=535 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=526 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Normal Baseline Grade to Normal Postbaseline Grade	6 participants	10 participants	9 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Normal Baseline Grade to Grade 1 postbaseline	39 participants	30 participants	25 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Normal Baseline Grade to Grade 2 postbaseline	8 participants	8 participants	4 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Normal Baseline Grade to Grade 3 postbaseline	0 participants	1 participants	1 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Normal Baseline Grade to Grade 4 postbaseline	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 1 Baseline to Normal postbaseline	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 1 Baseline to Grade 1 postbaseline	106 participants	126 participants	110 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade1 Baseline to Grade 2 postbaseline	128 participants	123 participants	123 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 1 Baseline to Grade 3 postbaseline	25 participants	17 participants	20 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 1 Baseline to Grade 4 postbaseline	2 participants	5 participants	4 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 2 Baseline to normal postbaseline	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 2 Baseline to Grade 1 postbaseline	8 participants	12 participants	14 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 2 Baseline to Grade 2 postbaseline	125 participants	135 participants	133 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 2 Baseline to Grade 3 postbaseline	48 participants	41 participants	47 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 2 Baseline to Grade 4 postbaseline	4 participants	9 participants	11 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 3 Baseline to Normal postbaseline	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 3 Baseline to Grade 1 postbaseline	0 participants	1 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 3 Baseline to Grade 2 postbaseline	12 participants	4 participants	10 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 3 Baseline to Grade 3 postbaseline	10 participants	8 participants	10 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 3 Baseline to Grade 4 postbaseline	5 participants	3 participants	2 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 4 Baseline to Normal postbaseline	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 4 Baseline to Grade 1 postbaseline	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 4 Baseline to Grade 2 postbaseline	0 participants	0 participants	1 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 4 Baseline to Grade 3 postbaseline	0 participants	1 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase Grade 4 Baseline to Grade 4 postbaseline	1 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm

Population: Safety population; Includes participants with baseline and postbaseline platelet laboratory test grade information

Improvement in platelets was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale.

Outcome measures

Outcome measures
Measure	Lenalidomide and Low-Dose Dexamethasone (Rd) n=527 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.	Lenalidomide and Dexamethasone Rd18 n=535 Participants Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those \> 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.	Melphalan + Prednisone + Thalidomide (MPT) n=526 Participants Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Normal Baseline Grade to Normal Postbaseline Grade	197 participants	197 participants	165 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Normal Baseline Grade to Grade 1 postbaseline	216 participants	211 participants	208 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Normal Baseline Grade to Grade 2 postbaseline	24 participants	30 participants	27 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Normal Baseline Grade to Grade 3 postbaseline	15 participants	12 participants	31 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Normal Baseline Grade to Grade 4 postbaseline	4 participants	5 participants	11 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade1 Baseline to Normal postbaseline Grade	1 participants	3 participants	6 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 1 Baseline to Grade 1 postbaseline	34 participants	38 participants	51 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 1 Baseline to Grade 2 postbaseline	15 participants	19 participants	7 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 1 Baseline to Grade 3 postbaseline	10 participants	12 participants	10 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 1 Baseline to Grade 4 postbaseline	2 participants	1 participants	1 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 2 Baseline to normal postbaseline Grade	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 2 Baseline to Grade 1 postbaseline	0 participants	1 participants	2 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 2 Baseline to Grade 2 postbaseline	3 participants	3 participants	1 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 2 Baseline to Grade 3 postbaseline	3 participants	2 participants	2 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 2 Baseline to Grade 4 postbaseline	1 participants	0 participants	2 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 3 Baseline to Normal postbaseline Grade	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 3 Baseline to Grade 1 postbaseline	0 participants	0 participants	0 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 3 Baseline to Grade 2 postbaseline	0 participants	0 participants	1 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 3 Baseline to Grade 3 postbaseline	0 participants	0 participants	1 participants
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. Grade 3 Baseline to Grade 4 postbaseline	2 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: From randomization to 24 May 2013

Improvement of infection rate by observing historical data compared to the data within clinical database as not analyzed.

Outcome measures

Outcome data not reported

Adverse Events

Lenalidomide and Low-Dose Dexamethasone (Rd)

Serious events: 378 serious events

Other events: 523 other events

Deaths: 0 deaths

Lenalidomide and Dexamethasone (Rd18)

Serious events: 308 serious events

Other events: 532 other events

Deaths: 0 deaths

Melphalan + Prednisone + Thalidomide (MPT)

Serious events: 270 serious events

Other events: 532 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Anne McClain, Senior Manager, Clinical Trial Disclosure

Celgene Corporation

Phone: 888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than one year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to ninety days; Investigator must delete confidential information before submission or defer publication to permit patent applications
Publication restrictions are in place

Restriction type: OTHER