Trial Outcomes & Findings for A Study to Compare MPR With MP in Newly Diagnosed Multiple Myeloma Subjects 65 Years Old or Older. (NCT NCT00405756)

Last Updated: 2017-01-11

Results Overview

Data as of 11 May 2010 cutoff. PFS was calculated as the time from randomization to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry \[EBMT/IBMTR/ABMTR\] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

459 participants

Primary outcome timeframe

up to 165 weeks

Results posted on

2017-01-11

Participant Flow

Data represents a May 11, 2010 data cut-off. The study is ongoing.

Of the 606 subjects screened for this study, 147 failed screening. Reasons for screen failures included: laboratory values not met (45 subjects); diagnostic criteria for measurable multiple myeloma not met (30 subjects); other inclusion/exclusion criteria not met (30 subjects); subject withdrawal of consent (14 subjects); and other (28 subjects).

Participant milestones

Participant milestones
Measure	MPR+R Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Double-blind Treatment STARTED	152	153	154
Double-blind Treatment Safety Population	150	152	153
Double-blind Treatment COMPLETED	0	0	0
Double-blind Treatment NOT COMPLETED	152	153	154
Open-label Extension STARTED	19	47	72
Open-label Extension COMPLETED	0	0	0
Open-label Extension NOT COMPLETED	19	47	72
Follow-up STARTED	75	90	88
Follow-up COMPLETED	0	0	0
Follow-up NOT COMPLETED	75	90	88

Reasons for withdrawal

Reasons for withdrawal
Measure	MPR+R Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Double-blind Treatment Ongoing in Double-blind Treatment	45	24	18
Double-blind Treatment Adverse Event	31	27	12
Double-blind Treatment Disease Progression	47	81	102
Double-blind Treatment Lack of Efficacy	1	4	2
Double-blind Treatment Withdrawal by Subject	15	9	10
Double-blind Treatment Lost to Follow-up	1	0	0
Double-blind Treatment Death	4	4	4
Double-blind Treatment Protocol Violation	1	0	2
Double-blind Treatment Other	7	4	4
Open-label Extension Ongoing in Open Label Period	7	15	25
Open-label Extension Adverse Event	1	3	7
Open-label Extension Disease Progression	8	23	26
Open-label Extension Withdrawal by Subject	2	3	3
Open-label Extension Death	1	2	4
Open-label Extension Other	0	1	7
Follow-up Ongoing in Follow-up Period	52	51	60
Follow-up Death	21	31	24
Follow-up Lost to Follow-up	2	8	4

Baseline Characteristics

A Study to Compare MPR With MP in Newly Diagnosed Multiple Myeloma Subjects 65 Years Old or Older.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Total n=459 Participants Total of all reporting groups
Age, Continuous	72.0 years STANDARD_DEVIATION 5.33 • n=5 Participants	72.1 years STANDARD_DEVIATION 5.20 • n=7 Participants	72.0 years STANDARD_DEVIATION 5.26 • n=5 Participants	72.0 years STANDARD_DEVIATION 5.25 • n=4 Participants
Age, Customized <=75 years	116 participants n=5 Participants	116 participants n=7 Participants	116 participants n=5 Participants	348 participants n=4 Participants
Age, Customized >75 years	36 participants n=5 Participants	37 participants n=7 Participants	38 participants n=5 Participants	111 participants n=4 Participants
Gender Female	81 Participants n=5 Participants	71 Participants n=7 Participants	79 Participants n=5 Participants	231 Participants n=4 Participants
Gender Male	71 Participants n=5 Participants	82 Participants n=7 Participants	75 Participants n=5 Participants	228 Participants n=4 Participants
Race/Ethnicity, Customized White	151 participants n=5 Participants	151 participants n=7 Participants	151 participants n=5 Participants	453 participants n=4 Participants
Race/Ethnicity, Customized Black	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Hispanic	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Asian / Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	4 participants n=4 Participants
Weight	73.5 kilograms STANDARD_DEVIATION 14.77 • n=5 Participants	72.0 kilograms STANDARD_DEVIATION 12.79 • n=7 Participants	72.1 kilograms STANDARD_DEVIATION 15.20 • n=5 Participants	72.5 kilograms STANDARD_DEVIATION 14.28 • n=4 Participants
Height	164.8 centimeter STANDARD_DEVIATION 9.81 • n=5 Participants	165.3 centimeter STANDARD_DEVIATION 9.33 • n=7 Participants	165.7 centimeter STANDARD_DEVIATION 9.79 • n=5 Participants	165.3 centimeter STANDARD_DEVIATION 9.63 • n=4 Participants
Systolic Blood Pressure	133.9 mmHg STANDARD_DEVIATION 17.71 • n=5 Participants	135.5 mmHg STANDARD_DEVIATION 18.60 • n=7 Participants	136.4 mmHg STANDARD_DEVIATION 20.13 • n=5 Participants	135.3 mmHg STANDARD_DEVIATION 18.83 • n=4 Participants
Diastolic Blood Pressure	78.5 mmHg STANDARD_DEVIATION 9.53 • n=5 Participants	77.4 mmHg STANDARD_DEVIATION 9.99 • n=7 Participants	78.8 mmHg STANDARD_DEVIATION 10.40 • n=5 Participants	78.2 mmHg STANDARD_DEVIATION 9.98 • n=4 Participants
Temperature	36.5 degrees centigrade STANDARD_DEVIATION 0.41 • n=5 Participants	36.5 degrees centigrade STANDARD_DEVIATION 0.38 • n=7 Participants	36.5 degrees centigrade STANDARD_DEVIATION 0.40 • n=5 Participants	36.5 degrees centigrade STANDARD_DEVIATION 0.40 • n=4 Participants
Pulse	76.0 beats per minute STANDARD_DEVIATION 9.77 • n=5 Participants	77.3 beats per minute STANDARD_DEVIATION 10.50 • n=7 Participants	76.3 beats per minute STANDARD_DEVIATION 10.80 • n=5 Participants	76.5 beats per minute STANDARD_DEVIATION 10.36 • n=4 Participants
Karnofsky Performance Scale	81.1 units on a scale STANDARD_DEVIATION 11.95 • n=5 Participants	82.2 units on a scale STANDARD_DEVIATION 11.71 • n=7 Participants	84.0 units on a scale STANDARD_DEVIATION 11.46 • n=5 Participants	82.4 units on a scale STANDARD_DEVIATION 11.74 • n=4 Participants
International Staging System (ISS) Stage I	28 participants n=5 Participants	32 participants n=7 Participants	28 participants n=5 Participants	88 participants n=4 Participants
International Staging System (ISS) Stage II	50 participants n=5 Participants	47 participants n=7 Participants	48 participants n=5 Participants	145 participants n=4 Participants
International Staging System (ISS) Stage III	74 participants n=5 Participants	74 participants n=7 Participants	78 participants n=5 Participants	226 participants n=4 Participants
Creatinine clearance >=60 ml/min	72 participants n=5 Participants	83 participants n=7 Participants	77 participants n=5 Participants	232 participants n=4 Participants
Creatinine clearance <60 ml/min	78 participants n=5 Participants	69 participants n=7 Participants	76 participants n=5 Participants	223 participants n=4 Participants
Creatinine clearance Missing	2 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	4 participants n=4 Participants
Beta2 Microglobulin >5.5 mg/L	74 participants n=5 Participants	78 participants n=7 Participants	67 participants n=5 Participants	219 participants n=4 Participants
Beta2 Microglobulin <=5.5 mg/L	77 participants n=5 Participants	75 participants n=7 Participants	87 participants n=5 Participants	239 participants n=4 Participants
Beta2 Microglobulin Missing	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Albumin >35 g/L	87 participants n=5 Participants	82 participants n=7 Participants	81 participants n=5 Participants	250 participants n=4 Participants
Albumin <= 35 g/L	63 participants n=5 Participants	70 participants n=7 Participants	72 participants n=5 Participants	205 participants n=4 Participants
Albumin Missing	2 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	4 participants n=4 Participants
C-reactive Protein >4 mg/L	65 participants n=5 Participants	56 participants n=7 Participants	64 participants n=5 Participants	185 participants n=4 Participants
C-reactive Protein <=4 mg/L	84 participants n=5 Participants	94 participants n=7 Participants	89 participants n=5 Participants	267 participants n=4 Participants
C-reactive Protein Missing	3 participants n=5 Participants	3 participants n=7 Participants	1 participants n=5 Participants	7 participants n=4 Participants
Multiple Myeloma Subtype Immunoglobulin A (IgA)	39 participants n=5 Participants	38 participants n=7 Participants	33 participants n=5 Participants	110 participants n=4 Participants
Multiple Myeloma Subtype Other	108 participants n=5 Participants	112 participants n=7 Participants	116 participants n=5 Participants	336 participants n=4 Participants
Multiple Myeloma Subtype Missing	5 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants	13 participants n=4 Participants
Plasma Cells in the Bone Marrow	39.8 percentage of plasma cells STANDARD_DEVIATION 24.79 • n=5 Participants	39.3 percentage of plasma cells STANDARD_DEVIATION 25.01 • n=7 Participants	37.9 percentage of plasma cells STANDARD_DEVIATION 23.65 • n=5 Participants	39.0 percentage of plasma cells STANDARD_DEVIATION 24.45 • n=4 Participants

PRIMARY outcome

Timeframe: up to 165 weeks

Population: Intent-to-treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Kaplan Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Central Adjudication Committee (CAC)	136.1 weeks Interval 86.14 to Upper limit not estimable because of the number of participants without progressive disease at data cut-off.	62.1 weeks Interval 56.14 to 72.14	56.1 weeks Interval 52.14 to 68.14

SECONDARY outcome

Timeframe: Approximately week 37 (start of cycle 10) to week 165

Population: Intent to treat (ITT) population of participants in Arms MPR+R and MPR+p who entered maintenance within the Double-blind Treatment Period

Data as of 11 May 2010 cutoff. PFS calculated from the start of the Maintenance period to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry \[EBMT/IBMTR/ABMTR\] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.

Outcome measures

Outcome measures
Measure	MPR+R n=88 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=94 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Kaplan Meier Estimates of Progression-free Survival (PFS) From Start of Maintenance Therapy Period Based on the Response Assessment by the Central Adjudication Committee (CAC)	112.0 weeks Interval 83.29 to Upper limit not estimable because of the number of participants without progressive disease at data cut-off.	32.3 weeks Interval 23.57 to 52.14	—

SECONDARY outcome

Timeframe: up to 177 weeks

Population: Intent to treat population

Data as of 11 May 2010 cutoff. Overall survival (OS) 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. 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 available, or clinical cut-off date, if it was earlier.

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Kaplan Meier Estimates of Overall Survival (OS)	NA weeks Not able to estimate since few participants died as of the May 11, 2010 cut-off.	NA weeks Interval 148.43 to Not able to estimate since few participants died as of the May 11, 2010 cut-off.	NA weeks Not able to estimate since few participants died as of the May 11, 2010 cut-off.

SECONDARY outcome

Timeframe: up to 165 weeks

Population: Intent to treat population

Data as of 11 May 2010 cutoff. TTP was the time between randomization and disease progression as determined by the CAC. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry \[EBMT/IBMTR/ABMTR\] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Kaplan Meier Estimates of Time to Progression (TTP) Based on the Response Assessment by the Central Adjudication Committee (CAC)	148.1 weeks Interval 100.0 to Upper limit not estimable because of the number of participants without progressive disease at data cut-off.	62.7 weeks Interval 57.14 to 74.14	61.3 weeks Interval 52.29 to 70.14

SECONDARY outcome

Timeframe: Up to 165 weeks

Population: Intent to treat population

Data as of 11 May 2010 cutoff. Best response was determined by the Central Assessment Committee (CAC) based on the European Group for Blood and Marrow Transplantation (EBMT) criteria: Complete Response (CR)-absence of serum and urine monoclonal paraprotein for 6 weeks, plus no increase in size or number of bone lesions, plus other factors); Partial Response (PR)-not all CR criteria, plus \>=50% reduction in serum monoclonal paraprotein plus others; Stable Disease (SD)- not PR or PD; Progressive Disease (PD)- reappearance of monoclonal paraprotein, bone lesions, other; Not Evaluable (NE).

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period Complete response (CR)	15 participants	5 participants	5 participants
Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period Partial response (PR)	102 participants	99 participants	72 participants
Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period Stable disease (SD)	28 participants	40 participants	70 participants
Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period Progressive disease (PD)	0 participants	2 participants	0 participants
Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period Response not evaluable (NE)	7 participants	7 participants	7 participants

SECONDARY outcome

Timeframe: Up to 66 weeks

Population: Participants who had a partial response (PR) or complete response (CR)

Data as of 11 May 2010 cutoff. Time to first response was defined as the time from start of treatment until first response as assessed by the Central Assessment Committee (CMC) based on European Group for Blood and Marrow Transplantation (EBMT) criteria.

Outcome measures

Outcome measures
Measure	MPR+R n=117 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=104 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=77 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Time to First Response	10.0 weeks Standard Deviation 7.40	9.3 weeks Standard Deviation 6.55	16.2 weeks Standard Deviation 11.59

SECONDARY outcome

Timeframe: Up to 149 weeks

Population: Population: Participants who achieved a partial response (PR) or complete response (CR).

Data as of 11 May 2010 cutoff. Duration of myeloma response was defined as the time from the initial response date to the earlier of progressive disease (PD) as determined by the CAC or death on study. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry \[EBMT/IBMTR/ABMTR\] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.

Outcome measures

Outcome measures
Measure	MPR+R n=117 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=104 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=77 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Kaplan Meier Estimates for Duration of Response as Determined by the Central Adjudication Committee (CAC)	121.6 weeks Interval 96.0 to Upper limit not estimable because of the number of participants without progressive disease at data cut-off.	56.1 weeks Interval 52.14 to 64.29	55.4 weeks Interval 44.14 to 76.14

SECONDARY outcome

Timeframe: Up to 168 weeks

Population: Intent to treat population

Data as of 11 May 2010 cutoff. Time to the next antimyeloma therapy was defined as time from randomization to the start of another non-protocol antimyeloma therapy. Participants 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	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Kaplan Meier Estimates for Time to Next Antimyeloma Therapy	128.9 weeks Interval 99.86 to Upper limit not estimable because of the number of participants who had not started a non-protocol anti-myeloma therapy at data cut-off.	66.1 weeks Interval 60.14 to 76.0	66.3 weeks Interval 61.14 to 72.43

SECONDARY outcome

Timeframe: Up to 169 weeks (Double-blind therapy period plus 4 weeks)

Population: Safety population

Data as of 11 May 2010 cutoff. Participant counts in different categories of TEAEs during the double-blind treatment period. A TEAE is as 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. Dose reduction includes reduction with or without interruption.

Outcome measures

Outcome measures
Measure	MPR+R n=150 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 AE related to Melphalan	140 participants	134 participants	126 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 Grade 3-4 AE related to Prednisone	32 participants	29 participants	22 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 Grade 5 AE related to Lenalidomide/Placebo	3 participants	2 participants	2 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 SAE related to Lenalidomide/Placebo	38 participants	32 participants	11 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 SAE related to Melphalan	27 participants	24 participants	11 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 AE leading to Prednisone dose interruption	28 participants	39 participants	15 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 adverse event (AE)	150 participants	151 participants	153 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 CTCAE grade 3-4 AE	137 participants	129 participants	107 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 CTCAE grade 5 AE	7 participants	6 participants	7 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 serious AE (SAE)	66 participants	62 participants	56 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 AE related to Lenaldomide/Placebo	148 participants	145 participants	131 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1AE related to Prednisone	87 participants	94 participants	93 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 Grade 3-4 AE related to Lenaldomide/Placebo	128 participants	117 participants	68 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 Grade 3-4 AE related to Melphalan	118 participants	110 participants	62 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 Grade 5 AE related to Melphalan	3 participants	1 participants	3 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 Grade 5 AE related to Prednisone	1 participants	1 participants	1 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 SAE related to Prednisone	19 participants	16 participants	5 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 AE leading to Lenalidomide/Placebo withdrawal	26 participants	24 participants	14 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 AE leading to Melphalan withdrawal	20 participants	19 participants	10 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 AE leading to Prednisone withdrawal	20 participants	19 participants	10 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 AE leading to Lenalidomide/Plac dose reduction	71 participants	70 participants	26 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 AE leading to Melphalan dose reduction	47 participants	58 participants	21 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 AE leading to Prednisone dose reduction	15 participants	7 participants	5 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 AE leading to Lenalidomide/Plac dose interrupt	92 participants	82 participants	51 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period >=1 AE leading to Melphalan dose interruption	5 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Data as of 11 May 2010 cutoff. EORTC QLC-C30 is a 30-item questionnaire to assess the quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); two used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better quality of life.

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale Cycle 7 - approximately Month 7 (n=96,108,110)	8.0 units on a scale Standard Deviation 24.95	8.1 units on a scale Standard Deviation 22.48	4.2 units on a scale Standard Deviation 23.92
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale Cycle 16 - approximately Month 16 (n=61,50,62)	10.7 units on a scale Standard Deviation 25.28	7.2 units on a scale Standard Deviation 26.29	8.1 units on a scale Standard Deviation 25.11
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale Cycle 4 - approximately Month 4 (n=114,121,125)	2.3 units on a scale Standard Deviation 26.13	5.6 units on a scale Standard Deviation 18.86	6.1 units on a scale Standard Deviation 19.41
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale Cycle 10 - approximately Month 10 (n=84,86,96)	12.4 units on a scale Standard Deviation 25.33	8.8 units on a scale Standard Deviation 24.70	6.2 units on a scale Standard Deviation 24.60
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale Cycle 13 - approximately Month 13 (n=70,70,82)	7.6 units on a scale Standard Deviation 28.32	8.8 units on a scale Standard Deviation 24.02	5.4 units on a scale Standard Deviation 22.80

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning.

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale Cycle 4 - approximately Month 4 (n=120,127,130)	1.9 units on a scale Standard Deviation 23.72	3.3 units on a scale Standard Deviation 21.64	4.5 units on a scale Standard Deviation 18.68
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale Cycle 7 - approximately Month 7 (n=100,112,112)	8.2 units on a scale Standard Deviation 22.71	8.1 units on a scale Standard Deviation 20.54	2.7 units on a scale Standard Deviation 23.20
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale Cycle 10 - approximately Month 10 (n=88,95,96)	8.9 units on a scale Standard Deviation 22.75	8.5 units on a scale Standard Deviation 25.62	5.1 units on a scale Standard Deviation 20.42
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale Cycle 13 - approximately Month 13 (n=75,74,83)	8.6 units on a scale Standard Deviation 24.04	9.7 units on a scale Standard Deviation 25.39	3.3 units on a scale Standard Deviation 20.30
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale Cycle 16 - approximately Month 16 (n=64,53,63)	10.0 units on a scale Standard Deviation 25.00	7.6 units on a scale Standard Deviation 22.66	1.1 units on a scale Standard Deviation 19.30

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale Cycle 13 - approximately Month 13 (n=74,74,82)	9.7 units on a scale Standard Deviation 40.36	11.7 units on a scale Standard Deviation 33.42	5.7 units on a scale Standard Deviation 30.68
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale Cycle 4 - approximately Month 4 (n=119,127,130)	1.8 units on a scale Standard Deviation 33.18	3.0 units on a scale Standard Deviation 30.75	7.4 units on a scale Standard Deviation 26.34
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale Cycle 7 - approximately Month 7 (n=99,112,113)	5.7 units on a scale Standard Deviation 35.57	8.0 units on a scale Standard Deviation 32.42	6.9 units on a scale Standard Deviation 31.16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale Cycle 10 - approximately Month 10 (n=86,95,95)	9.3 units on a scale Standard Deviation 35.76	7.5 units on a scale Standard Deviation 36.29	5.6 units on a scale Standard Deviation 31.29
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale Cycle 16 - approximately Month 16 (n=64,53,63)	12.2 units on a scale Standard Deviation 40.09	8.5 units on a scale Standard Deviation 34.22	7.1 units on a scale Standard Deviation 31.93

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale Cycle 4 - approximately Month 4 (n=115,125,128)	4.8 units on a scale Standard Deviation 25.00	2.7 units on a scale Standard Deviation 22.59	6.8 units on a scale Standard Deviation 18.75
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale Cycle 7 - approximately Month 7 (n=98,111,112)	8.8 units on a scale Standard Deviation 24.94	4.2 units on a scale Standard Deviation 20.38	5.0 units on a scale Standard Deviation 21.56
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale Cycle 10 - approximately Month 10 (n=86,92,97)	9.0 units on a scale Standard Deviation 23.28	1.6 units on a scale Standard Deviation 22.07	4.7 units on a scale Standard Deviation 22.05
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale Cycle 13 - approximately Month 13 (n=73,73,83)	8.2 units on a scale Standard Deviation 24.59	1.1 units on a scale Standard Deviation 21.78	6.6 units on a scale Standard Deviation 21.78
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale Cycle 16 - approximately Month 16 (n=63,52,63)	9.9 units on a scale Standard Deviation 23.23	-0.2 units on a scale Standard Deviation 21.57	6.9 units on a scale Standard Deviation 19.72

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale Cycle 4 - approximately Month 4 (n=115,125,128)	0.3 units on a scale Standard Deviation 21.51	-2.0 units on a scale Standard Deviation 21.33	1.3 units on a scale Standard Deviation 16.68
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale Cycle 7 - approximately Month 7 (n=98,111,113)	2.9 units on a scale Standard Deviation 22.31	0.1 units on a scale Standard Deviation 17.33	0.7 units on a scale Standard Deviation 18.42
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale Cycle 10 - approximately Month 10 (n=87,92,97)	1.0 units on a scale Standard Deviation 22.64	-4.4 units on a scale Standard Deviation 19.89	-2.7 units on a scale Standard Deviation 20.65
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale Cycle 13 - approximately Month 13 (n=73,73,83)	-0.0 units on a scale Standard Deviation 21.34	-3.0 units on a scale Standard Deviation 23.78	-1.4 units on a scale Standard Deviation 17.69
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale Cycle 16 - approximately Month 16 (n=63,52,63)	0.3 units on a scale Standard Deviation 22.29	-3.5 units on a scale Standard Deviation 27.48	-4.0 units on a scale Standard Deviation 18.13

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale Cycle 13 - approximately Month 13 (n=72,73,83)	11.8 units on a scale Standard Deviation 32.91	7.5 units on a scale Standard Deviation 29.80	6.2 units on a scale Standard Deviation 27.63
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale Cycle 16 - approximately Month 16 (n=63,52,63)	13.2 units on a scale Standard Deviation 33.35	6.1 units on a scale Standard Deviation 30.79	9.8 units on a scale Standard Deviation 28.66
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale Cycle 4 - approximately Month 4 (n=115,125,127)	5.1 units on a scale Standard Deviation 35.05	0.3 units on a scale Standard Deviation 26.60	6.0 units on a scale Standard Deviation 22.78
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale Cycle 7 - approximately Month 7 (n=98,111,112)	8.3 units on a scale Standard Deviation 33.87	4.4 units on a scale Standard Deviation 24.48	6.1 units on a scale Standard Deviation 26.57
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale Cycle 10 - approximately Month 10 (n=87,92,97)	10.9 units on a scale Standard Deviation 34.27	4.5 units on a scale Standard Deviation 29.87	4.1 units on a scale Standard Deviation 27.22

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale Cycle 7 - approximately Month 7 (n=100,112,110)	-7.6 units on a scale Standard Deviation 23.00	-9.5 units on a scale Standard Deviation 25.97	-5.7 units on a scale Standard Deviation 27.32
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale Cycle 10 - approximately Month 10 (n=87,95,95)	-7.5 units on a scale Standard Deviation 27.31	-7.5 units on a scale Standard Deviation 29.78	-6.9 units on a scale Standard Deviation 28.31
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale Cycle 4 - approximately Month 4 (n=120,127,129)	-3.0 units on a scale Standard Deviation 25.61	-5.5 units on a scale Standard Deviation 24.08	-5.1 units on a scale Standard Deviation 24.33
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale Cycle 13 - approximately Month 13 (n=74,74,82)	-7.1 units on a scale Standard Deviation 26.08	-10.7 units on a scale Standard Deviation 30.33	-7.5 units on a scale Standard Deviation 27.29
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale Cycle 16 - approximately Month 16 (n=64,53,62)	-10.0 units on a scale Standard Deviation 26.86	-9.7 units on a scale Standard Deviation 28.77	-4.1 units on a scale Standard Deviation 26.34

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale Cycle 4 - approximately Month 4 (n=120,127,130)	3.3 units on a scale Standard Deviation 19.40	-1.3 units on a scale Standard Deviation 17.14	-0.0 units on a scale Standard Deviation 17.36
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale Cycle 7 - approximately Month 7 (n=99,112,112)	0.5 units on a scale Standard Deviation 14.57	-0.7 units on a scale Standard Deviation 19.94	0.7 units on a scale Standard Deviation 14.73
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale Cycle 10 - approximately Month 10 (n=87,95,97)	1.9 units on a scale Standard Deviation 16.75	-1.4 units on a scale Standard Deviation 19.40	0.3 units on a scale Standard Deviation 14.23
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale Cycle 13 - approximately Month 13 (n=75,72,83)	0.7 units on a scale Standard Deviation 13.55	-3.0 units on a scale Standard Deviation 19.65	-0.4 units on a scale Standard Deviation 12.48
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale Cycle 16 - approximately Month 16 (n=64,52,62)	1.0 units on a scale Standard Deviation 12.90	-4.2 units on a scale Standard Deviation 18.65	-1.3 units on a scale Standard Deviation 9.21

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale Cycle 7 - approximately Month 7 (n=100,112,113)	-17.8 units on a scale Standard Deviation 36.18	-16.5 units on a scale Standard Deviation 33.45	-11.5 units on a scale Standard Deviation 33.49
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale Cycle 13 - approximately Month 13 (n=74,74,83)	-13.7 units on a scale Standard Deviation 40.48	-14.9 units on a scale Standard Deviation 33.28	-12.1 units on a scale Standard Deviation 27.46
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale Cycle 4 - approximately Month 4 (n=120,127,129)	-14.4 units on a scale Standard Deviation 32.76	-13.8 units on a scale Standard Deviation 33.60	-13.4 units on a scale Standard Deviation 29.32
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale Cycle 10 - approximately Month 10 (n=88,95,97)	-17.2 units on a scale Standard Deviation 34.78	-15.6 units on a scale Standard Deviation 35.30	-9.8 units on a scale Standard Deviation 31.71
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale Cycle 16 - approximately Month 16 (n=64,53,63)	-20.3 units on a scale Standard Deviation 33.92	-11.0 units on a scale Standard Deviation 33.00	-12.2 units on a scale Standard Deviation 29.96

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale Cycle 16 - approximately Month 16 (n=62,53,62)	-3.2 units on a scale Standard Deviation 29.39	-6.3 units on a scale Standard Deviation 32.07	1.6 units on a scale Standard Deviation 22.92
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale Cycle 13 - approximately Month 13 (n=73,73,81)	-5.0 units on a scale Standard Deviation 30.26	-2.3 units on a scale Standard Deviation 30.60	-0.0 units on a scale Standard Deviation 22.35
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale Cycle 4 - approximately Month 4 (n=117,126,126)	-2.6 units on a scale Standard Deviation 29.74	-6.4 units on a scale Standard Deviation 32.04	-0.0 units on a scale Standard Deviation 23.48
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale Cycle 7 - approximately Month 7 (n=100,110,110)	-1.7 units on a scale Standard Deviation 28.18	-8.5 units on a scale Standard Deviation 32.07	2.1 units on a scale Standard Deviation 20.82
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale Cycle 10 - approximately Month 10 (n=86,93,96)	-4.3 units on a scale Standard Deviation 30.60	-4.3 units on a scale Standard Deviation 35.87	3.8 units on a scale Standard Deviation 25.07

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale Cycle 4 - approximately Month 4 (n=118,124,128)	2.0 units on a scale Standard Deviation 33.56	-1.6 units on a scale Standard Deviation 31.77	-5.0 units on a scale Standard Deviation 27.77
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale Cycle 7 - approximately Month 7 (n=100,109,111)	-1.0 units on a scale Standard Deviation 29.76	-6.4 units on a scale Standard Deviation 27.02	-5.7 units on a scale Standard Deviation 32.06
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale Cycle 10 - approximately Month 10 (n=87,94,96)	-5.0 units on a scale Standard Deviation 28.99	-2.5 units on a scale Standard Deviation 25.04	-1.7 units on a scale Standard Deviation 32.58
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale Cycle 13 - approximately Month 13 (n=75,73,83)	-4.9 units on a scale Standard Deviation 29.86	0.9 units on a scale Standard Deviation 29.38	-6.8 units on a scale Standard Deviation 29.80
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale Cycle 16 - approximately Month 16 (n=64,53,63)	-4.7 units on a scale Standard Deviation 32.46	-0.6 units on a scale Standard Deviation 32.36	-3.7 units on a scale Standard Deviation 31.18

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale Cycle 13 - approximately Month 13 (n=75,72,83)	-6.2 units on a scale Standard Deviation 36.23	-8.8 units on a scale Standard Deviation 30.13	-4.8 units on a scale Standard Deviation 32.15
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale Cycle 4 - approximately Month 4 (n=119,125,130)	1.7 units on a scale Standard Deviation 36.54	1.9 units on a scale Standard Deviation 34.73	-5.6 units on a scale Standard Deviation 25.96
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale Cycle 7 - approximately Month 7 (n=99,111,111)	-3.7 units on a scale Standard Deviation 33.64	-5.7 units on a scale Standard Deviation 31.75	-5.7 units on a scale Standard Deviation 27.66
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale Cycle 10 - approximately Month 10 (n=87,93,96)	-5.0 units on a scale Standard Deviation 33.15	-5.4 units on a scale Standard Deviation 29.20	-8.0 units on a scale Standard Deviation 29.32
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale Cycle 16 - approximately Month 16 (n=64,52,63)	-7.8 units on a scale Standard Deviation 36.01	-16.0 units on a scale Standard Deviation 35.24	-6.4 units on a scale Standard Deviation 28.62

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale Cycle 4 - approximately Month 4 (n=114,124,128)	-1.8 units on a scale Standard Deviation 34.31	4.8 units on a scale Standard Deviation 30.86	-4.9 units on a scale Standard Deviation 27.45
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale Cycle 7 - approximately Month 7 (n=96,111,112)	-3.5 units on a scale Standard Deviation 36.35	0.6 units on a scale Standard Deviation 30.14	-2.7 units on a scale Standard Deviation 31.05
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale Cycle 10 - approximately Month 10 (n=86,93,97)	-5.0 units on a scale Standard Deviation 34.88	-1.1 units on a scale Standard Deviation 28.43	-1.7 units on a scale Standard Deviation 26.95
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale Cycle 13 - approximately Month 13 (n=73,73,81)	-5.0 units on a scale Standard Deviation 31.27	-2.7 units on a scale Standard Deviation 28.74	-3.3 units on a scale Standard Deviation 29.16
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale Cycle 16 - approximately Month 16 (n=63,51,62)	-1.6 units on a scale Standard Deviation 31.36	-5.2 units on a scale Standard Deviation 30.82	-2.2 units on a scale Standard Deviation 32.44

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale Cycle 4 - approximately Month 4 (n=115,125,124)	2.3 units on a scale Standard Deviation 28.85	1.9 units on a scale Standard Deviation 24.06	3.2 units on a scale Standard Deviation 25.65
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale Cycle 7 - approximately Month 7 (n=98,109,112)	3.4 units on a scale Standard Deviation 25.54	-1.2 units on a scale Standard Deviation 23.09	0.9 units on a scale Standard Deviation 22.13
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale Cycle 10 - approximately Month 10 (n=87,92,95)	1.1 units on a scale Standard Deviation 22.98	1.4 units on a scale Standard Deviation 20.91	-0.0 units on a scale Standard Deviation 21.19
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale Cycle 13 - approximately Month 13 (n=73,73,80)	5.5 units on a scale Standard Deviation 30.43	-1.4 units on a scale Standard Deviation 18.78	0.8 units on a scale Standard Deviation 18.35
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale Cycle 16 - approximately Month 16 (n=63,52,61)	10.6 units on a scale Standard Deviation 35.83	1.3 units on a scale Standard Deviation 19.75	0.5 units on a scale Standard Deviation 17.74

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale Cycle 4 - approximately Month 4 (n=111,123,125)	2.4 units on a scale Standard Deviation 24.91	-1.1 units on a scale Standard Deviation 19.06	-2.9 units on a scale Standard Deviation 18.93
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale Cycle 7 - approximately Month 7 (n=94,111,112)	2.1 units on a scale Standard Deviation 23.85	-0.6 units on a scale Standard Deviation 28.07	-2.1 units on a scale Standard Deviation 22.50
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale Cycle 10 - approximately Month 10 (n=84,92,97)	6.0 units on a scale Standard Deviation 21.44	0.7 units on a scale Standard Deviation 28.81	-1.7 units on a scale Standard Deviation 19.47
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale Cycle 13 - approximately Month 13 (n=70,72,83)	4.8 units on a scale Standard Deviation 21.45	-0.5 units on a scale Standard Deviation 28.80	-4.0 units on a scale Standard Deviation 26.75
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale Cycle 16 - approximately Month 16 (n=61,52,63)	1.6 units on a scale Standard Deviation 20.58	-0.6 units on a scale Standard Deviation 35.24	-5.3 units on a scale Standard Deviation 30.06

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Data as of 11 May 2010 cutoff. 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 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the disease symptoms scale = higher level of symptomatology.

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale Cycle 4 - approximately Month 4 (n=113,121,127)	-8.9 units on a scale Standard Deviation 19.56	-8.7 units on a scale Standard Deviation 19.13	-5.4 units on a scale Standard Deviation 15.83
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale Cycle 7 - approximately Month 7 (n=96,109,112)	-9.0 units on a scale Standard Deviation 20.64	-9.7 units on a scale Standard Deviation 23.25	-6.0 units on a scale Standard Deviation 20.81
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale Cycle 10 - approximately Month 10 (n=85,91,95)	-7.9 units on a scale Standard Deviation 23.00	-7.1 units on a scale Standard Deviation 23.85	-5.4 units on a scale Standard Deviation 18.79
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale Cycle 13 - approximately Month 13 (n=72,73,82)	-7.2 units on a scale Standard Deviation 25.91	-8.8 units on a scale Standard Deviation 24.90	-6.3 units on a scale Standard Deviation 21.84
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale Cycle 16 - approximately Month 16 (n=62,51,62)	-10.5 units on a scale Standard Deviation 23.87	-5.9 units on a scale Standard Deviation 25.79	-3.3 units on a scale Standard Deviation 20.67

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the side effects scale = higher level of symptomatology.

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale Cycle 4 - approximately Month 4 (n=113,120,125)	1.3 units on a scale Standard Deviation 13.37	0.1 units on a scale Standard Deviation 13.28	0.6 units on a scale Standard Deviation 12.67
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale Cycle 7 - approximately Month 7 (n=95,108,111)	0.4 units on a scale Standard Deviation 15.22	-1.7 units on a scale Standard Deviation 14.27	1.8 units on a scale Standard Deviation 12.94
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale Cycle 10 - approximately Month 10 (n=85,89,94)	-1.6 units on a scale Standard Deviation 14.46	0.0 units on a scale Standard Deviation 15.99	0.3 units on a scale Standard Deviation 12.61
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale Cycle 13 - approximately Month 13 (n=72,72,81)	-3.8 units on a scale Standard Deviation 15.61	-1.0 units on a scale Standard Deviation 14.59	0.3 units on a scale Standard Deviation 12.60
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale Cycle 16 - approximately Month 16 (n=62,50,61)	-2.1 units on a scale Standard Deviation 14.95	-2.9 units on a scale Standard Deviation 14.16	-0.9 units on a scale Standard Deviation 12.23

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the future perspective scale, higher score = better perspective of the future.

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale Cycle 4 - approximately Month 4 (n=112,121,124)	4.7 units on a scale Standard Deviation 23.74	4.3 units on a scale Standard Deviation 23.56	7.6 units on a scale Standard Deviation 22.38
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale Cycle 7 - approximately Month 7 (n=93,108,112)	14.6 units on a scale Standard Deviation 24.45	7.7 units on a scale Standard Deviation 23.86	9.8 units on a scale Standard Deviation 20.62
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale Cycle 10 - approximately Month 10 (n=83,88,97)	17.3 units on a scale Standard Deviation 27.84	6.6 units on a scale Standard Deviation 22.40	14.5 units on a scale Standard Deviation 21.73
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale Cycle 13 - approximately Month 13 (n=71,73,81)	17.3 units on a scale Standard Deviation 27.15	6.3 units on a scale Standard Deviation 23.78	11.9 units on a scale Standard Deviation 24.67
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale Cycle 16 - approximately Month 16 (n=62,52,62)	18.5 units on a scale Standard Deviation 25.30	7.7 units on a scale Standard Deviation 28.49	14.4 units on a scale Standard Deviation 26.62

SECONDARY outcome

Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16

Population: Intent to treat population

Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the body image scale, higher scores = better body image.

Outcome measures

Outcome measures
Measure	MPR+R n=152 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=153 Participants Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=154 Participants Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale Cycle 16 - approximately Month 16 (n=59,52,61)	3.4 units on a scale Standard Deviation 32.58	6.4 units on a scale Standard Deviation 41.25	2.7 units on a scale Standard Deviation 28.08
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale Cycle 4 - approximately Month 4 (n=110,117,119)	2.1 units on a scale Standard Deviation 35.36	-0.3 units on a scale Standard Deviation 37.27	4.5 units on a scale Standard Deviation 25.65
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale Cycle 7 - approximately Month 7 (n=88,104,108)	3.8 units on a scale Standard Deviation 33.32	2.6 units on a scale Standard Deviation 37.94	5.2 units on a scale Standard Deviation 27.78
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale Cycle 10 - approximately Month 10 (n=79,83,94)	7.6 units on a scale Standard Deviation 33.32	-4.0 units on a scale Standard Deviation 43.69	3.9 units on a scale Standard Deviation 26.72
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale Cycle 13 - approximately Month 13 (n=68,72,79)	1.0 units on a scale Standard Deviation 31.01	-0.5 units on a scale Standard Deviation 44.23	5.1 units on a scale Standard Deviation 32.51

Adverse Events

MPR+R

Serious events: 66 serious events

Other events: 149 other events

Deaths: 0 deaths

MPR+p

Serious events: 62 serious events

Other events: 151 other events

Deaths: 0 deaths

MPp+p

Serious events: 56 serious events

Other events: 152 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Associate Director, Clinical Trials Disclosure

Celgene Corporation

Phone: 1-888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Upon investigator submission of a publication or presentation to Celgene, Celgene shall complete its review within 60 days after receipt of the proposed publication or presentation. Upon Celgene's request, proposed publication or presentation will be delayed up to 90 additional days to enable Celgene to secure adequate intellectual property protection of property of Celgene that would be affected by such proposed publication or presentation.
Publication restrictions are in place

Restriction type: OTHER

Measure	MPR+R n=150 participants at risk Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPR+p n=152 participants at risk Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	MPp+p n=153 participants at risk Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Blood and lymphatic system disorders Neutropenia	78.0% 117/150 • Number of events 951 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	76.3% 116/152 • Number of events 807 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	51.0% 78/153 • Number of events 398 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Blood and lymphatic system disorders Anaemia	66.0% 99/150 • Number of events 417 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	59.9% 91/152 • Number of events 351 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	53.6% 82/153 • Number of events 293 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Blood and lymphatic system disorders Thrombocytopenia	68.7% 103/150 • Number of events 514 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	65.8% 100/152 • Number of events 532 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	44.4% 68/153 • Number of events 268 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Blood and lymphatic system disorders Leukopenia	36.0% 54/150 • Number of events 418 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	38.2% 58/152 • Number of events 449 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	32.0% 49/153 • Number of events 237 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Gastrointestinal disorders Nausea	24.7% 37/150 • Number of events 65 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	25.7% 39/152 • Number of events 66 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	33.3% 51/153 • Number of events 93 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Gastrointestinal disorders Constipation	32.7% 49/150 • Number of events 80 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	25.7% 39/152 • Number of events 66 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	24.2% 37/153 • Number of events 57 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Gastrointestinal disorders Diarrhoea	28.7% 43/150 • Number of events 124 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	23.7% 36/152 • Number of events 62 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	24.2% 37/153 • Number of events 50 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Gastrointestinal disorders Vomiting	10.0% 15/150 • Number of events 24 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	11.8% 18/152 • Number of events 27 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	12.4% 19/153 • Number of events 30 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Gastrointestinal disorders Abdominal pain upper	8.7% 13/150 • Number of events 18 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	4.6% 7/152 • Number of events 9 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	8.5% 13/153 • Number of events 19 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Gastrointestinal disorders Abdominal pain	10.7% 16/150 • Number of events 25 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	5.9% 9/152 • Number of events 9 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	3.9% 6/153 • Number of events 7 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Gastrointestinal disorders Dyspepsia	8.0% 12/150 • Number of events 17 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	3.9% 6/152 • Number of events 6 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	5.2% 8/153 • Number of events 10 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Gastrointestinal disorders Dry mouth	8.0% 12/150 • Number of events 14 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	4.6% 7/152 • Number of events 8 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	2.6% 4/153 • Number of events 6 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
General disorders Fatigue	30.7% 46/150 • Number of events 110 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	33.6% 51/152 • Number of events 97 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	37.3% 57/153 • Number of events 101 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
General disorders Pyrexia	21.3% 32/150 • Number of events 47 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	25.0% 38/152 • Number of events 63 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	17.6% 27/153 • Number of events 33 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
General disorders Oedema peripheral	20.0% 30/150 • Number of events 47 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	23.0% 35/152 • Number of events 59 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	16.3% 25/153 • Number of events 35 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
General disorders Asthenia	22.0% 33/150 • Number of events 67 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	14.5% 22/152 • Number of events 38 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	16.3% 25/153 • Number of events 39 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
General disorders Oedema	5.3% 8/150 • Number of events 11 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	9.2% 14/152 • Number of events 16 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	4.6% 7/153 • Number of events 11 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Musculoskeletal and connective tissue disorders Bone pain	30.7% 46/150 • Number of events 96 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	29.6% 45/152 • Number of events 77 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	33.3% 51/153 • Number of events 76 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Musculoskeletal and connective tissue disorders Back pain	10.7% 16/150 • Number of events 16 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	11.2% 17/152 • Number of events 23 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	19.0% 29/153 • Number of events 38 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	13.3% 20/150 • Number of events 37 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	11.8% 18/152 • Number of events 22 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	13.7% 21/153 • Number of events 38 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Musculoskeletal and connective tissue disorders Arthralgia	7.3% 11/150 • Number of events 12 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	14.5% 22/152 • Number of events 28 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	11.1% 17/153 • Number of events 23 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Musculoskeletal and connective tissue disorders Muscle spasms	12.7% 19/150 • Number of events 34 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	11.2% 17/152 • Number of events 36 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	5.9% 9/153 • Number of events 9 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Musculoskeletal and connective tissue disorders Pain in extremity	8.7% 13/150 • Number of events 18 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	3.9% 6/152 • Number of events 11 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	6.5% 10/153 • Number of events 12 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Infections and infestations Nasopharyngitis	15.3% 23/150 • Number of events 34 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	13.8% 21/152 • Number of events 32 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	17.0% 26/153 • Number of events 34 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Infections and infestations Upper respiratory tract infection	10.7% 16/150 • Number of events 25 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	12.5% 19/152 • Number of events 23 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	9.8% 15/153 • Number of events 20 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Infections and infestations Bronchitis	10.7% 16/150 • Number of events 25 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	9.9% 15/152 • Number of events 20 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	7.8% 12/153 • Number of events 16 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Infections and infestations Urinary tract infection	8.0% 12/150 • Number of events 15 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	7.2% 11/152 • Number of events 15 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	7.2% 11/153 • Number of events 13 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Metabolism and nutrition disorders Anorexia	16.0% 24/150 • Number of events 37 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	23.7% 36/152 • Number of events 54 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	15.0% 23/153 • Number of events 26 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Metabolism and nutrition disorders Hyperglycaemia	8.0% 12/150 • Number of events 42 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	6.6% 10/152 • Number of events 32 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	11.1% 17/153 • Number of events 46 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Metabolism and nutrition disorders Hypokalaemia	11.3% 17/150 • Number of events 21 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	7.9% 12/152 • Number of events 23 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	3.9% 6/153 • Number of events 6 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Metabolism and nutrition disorders Hypocalcaemia	6.7% 10/150 • Number of events 12 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	5.3% 8/152 • Number of events 18 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	6.5% 10/153 • Number of events 25 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Nervous system disorders Dizziness	10.0% 15/150 • Number of events 22 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	13.2% 20/152 • Number of events 21 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	10.5% 16/153 • Number of events 21 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Nervous system disorders Paraesthesia	10.0% 15/150 • Number of events 19 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	6.6% 10/152 • Number of events 17 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	3.9% 6/153 • Number of events 7 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Nervous system disorders Headache	7.3% 11/150 • Number of events 29 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	10.5% 16/152 • Number of events 26 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	13.7% 21/153 • Number of events 21 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Nervous system disorders Peripheral sensory neuropathy	7.3% 11/150 • Number of events 14 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	5.9% 9/152 • Number of events 13 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	3.3% 5/153 • Number of events 10 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Nervous system disorders Dysgeusia	4.0% 6/150 • Number of events 9 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	6.6% 10/152 • Number of events 13 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	4.6% 7/153 • Number of events 7 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Skin and subcutaneous tissue disorders Rash	20.0% 30/150 • Number of events 62 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	27.6% 42/152 • Number of events 63 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	7.8% 12/153 • Number of events 13 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Skin and subcutaneous tissue disorders Pruritus	10.7% 16/150 • Number of events 24 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	8.6% 13/152 • Number of events 16 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	6.5% 10/153 • Number of events 11 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Respiratory, thoracic and mediastinal disorders Cough	22.7% 34/150 • Number of events 47 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	17.8% 27/152 • Number of events 33 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	13.7% 21/153 • Number of events 29 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.3% 20/150 • Number of events 34 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	9.9% 15/152 • Number of events 20 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	11.8% 18/153 • Number of events 22 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Respiratory, thoracic and mediastinal disorders Epistaxis	5.3% 8/150 • Number of events 15 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	4.6% 7/152 • Number of events 10 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	7.2% 11/153 • Number of events 16 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	4.0% 6/150 • Number of events 9 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	5.9% 9/152 • Number of events 10 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	5.9% 9/153 • Number of events 11 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Investigations Blood creatinine increased	8.0% 12/150 • Number of events 21 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	3.9% 6/152 • Number of events 13 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	11.1% 17/153 • Number of events 33 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Investigations Weight decreased	5.3% 8/150 • Number of events 10 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	8.6% 13/152 • Number of events 18 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	5.9% 9/153 • Number of events 11 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Psychiatric disorders Insomnia	11.3% 17/150 • Number of events 18 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	13.2% 20/152 • Number of events 23 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	14.4% 22/153 • Number of events 35 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Psychiatric disorders Depression	6.0% 9/150 • Number of events 12 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	11.2% 17/152 • Number of events 18 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	6.5% 10/153 • Number of events 10 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Vascular disorders Hypertension	2.7% 4/150 • Number of events 5 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	5.9% 9/152 • Number of events 11 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	8.5% 13/153 • Number of events 23 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Vascular disorders Hypotension	6.7% 10/150 • Number of events 13 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	2.6% 4/152 • Number of events 4 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	6.5% 10/153 • Number of events 10 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Ear and labyrinth disorders Vertigo	8.7% 13/150 • Number of events 23 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	6.6% 10/152 • Number of events 13 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)	9.2% 14/153 • Number of events 25 • Up to 169 weeks (Double-blind therapy period plus 4 weeks)