Trial Outcomes & Findings for A Study of Lenalidomide Versus Placebo in Subjects With Transfusion Dependent Anemia in Lower Risk Myelodysplastic Syndrome (MDS) Without Del 5q (NCT NCT01029262)

NCT ID: NCT01029262

Last Updated: 2019-06-25

Results Overview

The percentage of participants who achieved the 56-day RBC transfusion independent (TI) response was defined as the absence of any RBC transfusions during any consecutive "rolling" 56-day interval within the double-blind treatment phase (ie, Days 2 (Day 1 is the first study drug day) to 57, Days 3 to 58, etcetera). The double-blind treatment phase was defined as the period between the 1st dosing up until 28 days after the last study drug dose

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 239 participants
• Primary outcome timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
• Results posted on: 2019-06-25

Participant Flow

239 participants were randomized at sites located in Europe (185), North America (24), Asia/Pacific (13) and the Middle East (17).

Participants must have had transfusion-dependent anemia defined as having an average transfusion need of at least 2 units of packed red blood cells (pRBCs) per 28 days during the 112 days preceding randomization; No consecutive 56-day period that was RBC-transfusion-free during the 112 days preceding randomization; hemoglobin levels ≤ 9.5 g/dL.

Participant milestones

Measure	Placebo Participants received 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide Participants received lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Participants received lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Overall Study STARTED	79	160
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	79	160

Reasons for withdrawal

Measure	Placebo Participants received 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide Participants received lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Participants received lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Overall Study Adverse Event	9	52
Overall Study Lack of therapeutic effect	57	76
Overall Study Withdrawal by Subject	10	17
Overall Study Protocol Violation	2	3
Overall Study Miscellaneous	1	9
Overall Study Death	0	3

Baseline Characteristics

A Study of Lenalidomide Versus Placebo in Subjects With Transfusion Dependent Anemia in Lower Risk Myelodysplastic Syndrome (MDS) Without Del 5q

Baseline characteristics by cohort

Measure	Placebo n=79 Participants Participants received 3 placebo capsules by mouth daily for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=160 Participants Participants receieved lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.	Total n=239 Participants Total of all reporting groups
Age, Continuous	68.9 years STANDARD_DEVIATION 8.26 • n=5 Participants	70.0 years STANDARD_DEVIATION 8.19 • n=7 Participants	69.6 years STANDARD_DEVIATION 8.21 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	52 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	108 Participants n=7 Participants	162 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	69 Participants n=5 Participants	133 Participants n=7 Participants	202 Participants n=5 Participants
Race/Ethnicity, Customized Japanese	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Race Not Disclosed	4 Participants n=5 Participants	15 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Packed RBC (pRBC) Transfusion Burden	3.4 pRBC units/28 days STANDARD_DEVIATION 1.37 • n=5 Participants	3.4 pRBC units/28 days STANDARD_DEVIATION 1.23 • n=7 Participants	3.4 pRBC units/28 days STANDARD_DEVIATION 1.28 • n=5 Participants
International Prognostic Scoring System (IPSS) Investigator Determined Low	30 Participants n=5 Participants	85 Participants n=7 Participants	115 Participants n=5 Participants
International Prognostic Scoring System (IPSS) Investigator Determined Intermediate 1	49 Participants n=5 Participants	75 Participants n=7 Participants	124 Participants n=5 Participants
World Health Organization Classification 2008 of MDS by Central Review Refractory anemia (RA)	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
World Health Organization Classification 2008 of MDS by Central Review Refractory cytopenia unilineage dysplasia (RCUD)	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
World Health Organization Classification 2008 of MDS by Central Review RA with ringed sideroblasts (RARS)	7 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants
World Health Organization Classification 2008 of MDS by Central Review Refractory cytopenia multilineage dysplasia (RCMD)	59 Participants n=5 Participants	115 Participants n=7 Participants	174 Participants n=5 Participants
World Health Organization Classification 2008 of MDS by Central Review Refractory anemia with excess blasts-1 (RAEB-1)	12 Participants n=5 Participants	27 Participants n=7 Participants	39 Participants n=5 Participants
Prior Erythropoiesis-stimulating Agent (ESA) Treatment Yes	63 Participants n=5 Participants	125 Participants n=7 Participants	188 Participants n=5 Participants
Prior Erythropoiesis-stimulating Agent (ESA) Treatment No	16 Participants n=5 Participants	35 Participants n=7 Participants	51 Participants n=5 Participants
Hemoglobin	8.7 g/dL STANDARD_DEVIATION 1.37 • n=5 Participants	8.7 g/dL STANDARD_DEVIATION 1.23 • n=7 Participants	8.7 g/dL STANDARD_DEVIATION 1.28 • n=5 Participants
Gene Expression Signature	3 Participants n=5 Participants	14 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.

Population: The Intent-to-Treat (ITT) population includes all participants who were randomized to either lenalidomide or placebo.

The percentage of participants who achieved the 56-day RBC transfusion independent (TI) response was defined as the absence of any RBC transfusions during any consecutive "rolling" 56-day interval within the double-blind treatment phase (ie, Days 2 (Day 1 is the first study drug day) to 57, Days 3 to 58, etcetera). The double-blind treatment phase was defined as the period between the 1st dosing up until 28 days after the last study drug dose

Outcome measures

Measure	Placebo n=79 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=160 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)	2.5 percentage of participants	26.9 percentage of participants

PRIMARY outcome

Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.

Population: Analysis population includes ITT participants with an erythroid gene expression signature.

The percentage of participants who achieved the 56-day RBC TI response was defined as the absence of any RBC transfusions during any consecutive "rolling" 56-day interval within the double-blind treatment phase (ie, Days 2 (Day 1 is the first study drug day) to 57, Days 3 to 58, etcetera). A participant who achieved at least a 56-day RBC-transfusion-independent response was considered a 56-day RBC-TI responder.

Outcome measures

Measure	Placebo n=3 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=14 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Percentage of Participants With a Erythroid Gene Signature Who Achieved RBC Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)	0.0 percentage of participants	7.1 percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.

Population: The ITT population includes all participants who were randomized to either lenalidomide or placebo.

The 168-day RBC-transfusion-independent response was defined as the absence of any RBC transfusion during any consecutive "rolling" 168 days during the treatment period, for example Days 2 (Day 1 is the first study drug day) to 169, Days 3 to 170, Days 4 to 171, etcetera. A responder was defined as a participant who had a ≥ 168 consecutive days of RBC-transfusion-free period after the first dose of study drug in the treatment phase.

Outcome measures

Measure	Placebo n=79 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=160 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Percentage of Participants Who Achieved RBC Transfusion Independence With a Duration of ≥ 24 Weeks (168 Days) as Determined by the Sponsor	0.0 percentage of participants	17.5 percentage of participants

SECONDARY outcome

Timeframe: Response was assessed up to the end of treatment; up to the data cut-off date of 17 Mar 2014.

Population: The analysis was conducted only for those participants who achieved a 56-day transfusion independence response according to the sponsor's assessment. Responders in the intent to treat population.

The duration of the first 56-day RBC transfusion-independence response was calculated for those who achieved a response and was dependent on whether a subsequent RBC transfusion was given after the transfusion-free period (response):

• For those who received a subsequent RBC transfusion after the response starts, the duration of response was not censored, and was calculated as response duration = last day of response - first day of response +1 where the last day of response was defined as 1 day before the first RBC transfusion which was given at 56 days or more after the response starts.
• For those who did not receive a subsequent RBC transfusion after the response started, the end day of the response was censored and duration of the response was calculated as response duration = date of last RBC transfusion assessment - first day of response+ 1. A responder was a participant who had a ≥ 56 consecutive days of RBC-transfusion-free period after the first study drug treatment period

Outcome measures

Measure	Placebo n=1 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=41 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Kaplan Meier Estimates of Duration of 56-day RBC Transfusion Independence Response as Determined by the Sponsor	NA weeks Only one placebo participant achieved the response and the response end date was censored	30.9 weeks Interval 20.7 to 59.1

SECONDARY outcome

Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.

Population: The ITT population includes all participants who were randomized to either lenalidomide or placebo.

A participant was considered as having achieved an erythroid response if the participant either:

• had a hemoglobin (Hgb) increase ≥1.5 g/dL compared to baseline and confirmed by another central laboratory hemoglobin value at 4 to 8 weeks after the first Hgb measurement that also increased ≥1.5 g/dL. All Hgb values during this time interval must have had a ≥ 1.5 g/dL increase (ie, no central laboratory Hgb increase during this timeframe could be less <1.5 g/dL) OR - had a 50% reduction in the number of the RBC transfusion units over any consecutive 56 days period compared to the baseline transfusion burden.

The baseline transfusion burden is the number of units over 112 days by the randomization divided by 2. Only transfusions given for a pre-transfusion Hgb value of 9 g/dL or less were used in this response assessment.

Outcome measures

Measure	Placebo n=79 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=160 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Percentage of Participants Who Achieved an Erythroid Response Based on the Modified International Working Group (IWG) 2006 Criteria	30.4 percentage of participants	38.8 percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug until 28 days after the last dose of study drug, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.

Population: The analysis was conducted only for those participants who achieved a 56-day TI response according to the sponsor's assessment. Responders in the intent to treat population.

The time to the first 56-day RBC-transfusion-independent response was calculated for participants who achieved a response. The day from the first dose of study drug to the date at which RBC-transfusion-independence starts was achieved and calculated using: Start date of the first response period - the date of the first study drug +1. A responder was defined as a participant who had a ≥ 56 consecutive days of RBC-transfusion-free period after the first dose of study drug in the treatment phase.

Outcome measures

Measure	Placebo n=1 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=41 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Time to 56-Day RBC-Transfusion-Independent (TI) Response as Determined by the Sponsor	0.3 weeks Interval 0.3 to 0.3	10.1 weeks Interval 0.3 to 23.6

SECONDARY outcome

Timeframe: From randomization to final data cut-off date of 03 Jul 2018; median follow up time for progression to AML was 2.3 years (range = 0 to 5.0 years) in the placebo arm and 2.6 years (range = 0 to 6.4 years) in the lenalidomide arm.

Population: ITT population includes all participants who were randomized and received either lenalidomide or placebo. One participant in the placebo arm was diagnosed as having AML before enrollment and was excluded from all analyses of progression to AML.

Progression to AML is part of the natural course of MDS and is a manifestation of disease progression. The time to progress to AML was calculated from the day of randomization to the first day when AML was diagnosed. Participants who died without AML were censored at the date of death. The participants who were lost to follow-up were censored at the last known day when participants did not have AML. Participants who did not progress to AML at the last follow-up contact were censored at the day of the last follow-up contact.

Outcome measures

Measure	Placebo n=78 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=160 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Kaplan Meier Estimates for Progression to Acute Myeloid Leukemia (AML)	NA years Since only a few patients progressed to AML during the observed time frame, median time of progression to AML could not be estimated.	NA years Interval 5.2 to Since only a few patients progressed to AML during the observed time frame, median time of progression to AML could not be estimated.

SECONDARY outcome

Timeframe: From randomization to final data cut-off date of 03 July 2018; maximum survival follow up was 6.4 years

Population: The ITT population includes all participants who were randomized to either lenalidomide or placebo.

Overall survival was assessed using the time between randomization and the date of death or date of censoring. Participants who were alive at a data cutoff date and participants who were lost to follow-up were censored at the last date when participants were known to be alive.

Outcome measures

Measure	Placebo n=79 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=160 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Kaplan Meier Estimate for Overall Survival (OS)	3.0 years Interval 2.3 to Placebo upper limit not estimable.	3.8 years Interval 2.9 to 4.8

SECONDARY outcome

Timeframe: From the first dose of study drug through 28 days after discontinuation from the study treatment; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide arm and 529 days in the placebo arm.

Population: Safety population includes all participants who received at least 1 dose of study drug.

A TEAE was defined as an AE that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug.

A serious adverse event (SAE) is any:

• Death;
• Life-threatening event;
• Any inpatient hospitalization or prolongation of existing hospitalization;
• Persistent or significant disability or incapacity;
• Congenital anomaly or birth defect;
• Any other important medical event

The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 3.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.

Outcome measures

Measure	Placebo n=79 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=160 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE Leading to Dose Reduction	1 Participants	10 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) At least 1 TEAE	74 Participants	160 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Treatment Related AE (TEAE)	42 Participants	144 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Treatment related TEAE Causing Discontinuation	3 Participants	40 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE Leading to Dose Interruption	11 Participants	89 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE Leading to Dose Interruption & Reduction	5 Participants	68 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE Leading to Discontinuation of Study Drug	9 Participants	51 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Serious TEAE	16 Participants	62 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 Treatment-Related Serious TEAE	3 Participants	25 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 Serious TEAE Leading to Dose Reduction	0 Participants	1 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 serious TEAE leading to dose interruption	4 Participants	21 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 SAE Causing Dose Interruption & reduction	1 Participants	3 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 Serious TEAE Leading to Stopping of Study Drug	4 Participants	24 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 Grade (GR) 3-4 TEAE	35 Participants	139 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 GR 3-4 Related TEAE	16 Participants	127 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 GR 3-4 Leading to Dose Reduction	1 Participants	8 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 GR 3-4 TEAE Leading to Dose Interruption	9 Participants	80 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 GR 3-4 TEAE dose Interruption &reduction	4 Participants	64 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 GR 3-4 TEAE Leading to Stopping of Study Med	6 Participants	41 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 GR 5 TEAE	2 Participants	6 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 GR Treatment Related 5 TEAE	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12, (±3 days), Week 24, (±3 days), Week 36, (±3 days), and Week 48 (±3 days); up to data cut-off of 17 Mar 2014

Population: Analyses were performed based on the Health Related Quality of Life (HRQoL) evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Data is available up to Week 48 due to small sample after that.

The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. A participant was considered compliant at a visit if at least 15 out of the QLQ-C30 items in the questionnaire were checked.

Outcome measures

Measure	Placebo n=79 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=160 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 Baseline	88.6 percentage of participants	90 percentage of participants
Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 Week 12	78.5 percentage of participants	83.8 percentage of participants
Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 Week 24	80.6 percentage of participants	85.8 percentage of participants
Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 Week 36	100 percentage of participants	80.5 percentage of participants
Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 Week 48	50 percentage of participants	71.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

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

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24 Week 12	0.6 units on a scale Standard Deviation 17.53	2.4 units on a scale Standard Deviation 28.26
Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24 Week 24	7.6 units on a scale Standard Deviation 20.74	-1.5 units on a scale Standard Deviation 26.42

SECONDARY outcome

Timeframe: Baseline and Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the Health Related Quality of Life (HRQoL) evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

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

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24 Week 12	0.6 units on a scale Standard Deviation 28.06	2.2 units on a scale Standard Deviation 29.92
Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24 Week 24	4.3 units on a scale Standard Deviation 26.57	1.2 units on a scale Standard Deviation 26.26

SECONDARY outcome

Timeframe: Baseline and Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the Health Related Quality of Life (HRQoL) evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

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

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24 Week 12	-1.4 units on a scale Standard Deviation 15.76	-2.1 units on a scale Standard Deviation 18.09
Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24 Week 24	-5.7 units on a scale Standard Deviation 14.84	-0.4 units on a scale Standard Deviation 18.19

SECONDARY outcome

Timeframe: Baseline and Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

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

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24 Week 12	-2.1 units on a scale Standard Deviation 20.18	-1.4 units on a scale Standard Deviation 24.35
Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24 Week 24	-4.1 units on a scale Standard Deviation 20.25	-2.4 units on a scale Standard Deviation 27.87

SECONDARY outcome

Timeframe: Baseline and Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

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

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24 Week 12	1.2 units on a scale Standard Deviation 18.70	-1.4 units on a scale Standard Deviation 22.39
Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24 Week 24	-7.1 units on a scale Standard Deviation 20.78	0.8 units on a scale Standard Deviation 20.06

SECONDARY outcome

Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 Week 12	-0.464 units on a scale Interval -6.562 to 5.635	3.497 units on a scale Interval -0.631 to 7.624
Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 Week 24	7.376 units on a scale Interval 0.99 to 13.762	0.196 units on a scale Interval -4.505 to 4.897

SECONDARY outcome

Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

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

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 Week 12	1.696 units on a scale Interval -5.313 to 8.706	3.374 units on a scale Interval -1.369 to 8.117
Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 Week 24	5.998 units on a scale Interval -1.174 to 13.171	-0.206 units on a scale Interval -5.557 to 5.146

SECONDARY outcome

Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Physical Functioning was scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 Week 12	0.732 units on a scale Interval -4.939 to 3.475	-2.919 units on a scale Interval -5.768 to -0.071
Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 Week 24	-5.451 units on a scale Interval -10.046 to -0.85	-1.484 units on a scale Interval -4.861 to 1.892

SECONDARY outcome

Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Global Health Status/QOL scale was scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Mean Change From Baseline in the Global Health Status/QoL Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 Week 12	-1.201 units on a scale Interval -6.401 to 3.999	-2.690 units on a scale Interval -6.211 to 0.831
Mean Change From Baseline in the Global Health Status/QoL Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 Week 24	-4.502 units on a scale Interval -10.33 to 1.326	-2.441 units on a scale Interval -6.761 to 1.88

SECONDARY outcome

Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

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

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24 Week 12	1.458 units on a scale Interval -3.621 to 6.536	-1.876 units on a scale Interval -5.307 to 1.556
Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24 Week 24	-6.746 units on a scale Interval -12.228 to -1.26	-1.129 units on a scale Interval -5.174 to 2.917

SECONDARY outcome

Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the Health Related Quality of Life (HRQoL) evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. Improvement means at least 10 points better compared to baseline

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Percentage of Participants With a Clinically Meaningful Improvement in QOL (EORTC QLQ-C-30 Scale) From Baseline in Fatigue Domain at Weeks 12 and 24 Week 12	30.4 percentage of participants	39.3 percentage of participants
Percentage of Participants With a Clinically Meaningful Improvement in QOL (EORTC QLQ-C-30 Scale) From Baseline in Fatigue Domain at Weeks 12 and 24 Week 24	29.8 percentage of participants	38.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom). Improvement means at least 10 points better compared to baseline.

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Dyspnea Domain at Weeks 12 and 24 Week 12	19.6 percentage of participants	21.3 percentage of participants
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Dyspnea Domain at Weeks 12 and 24 Week 24	12.8 percentage of participants	20.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment with the EORTC QLQ-C-30. Only those with available data at baseline and each time point are included.

The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. A change of at least 10 points on the standardized domain scores was required for it to be considered clinically meaningful.

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline Within the Physical Functioning Domain at Weeks 12 and 24 Week 12	26.8 percentage of participants	16.4 percentage of participants
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline Within the Physical Functioning Domain at Weeks 12 and 24 Week 24	12.8 percentage of participants	24.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment with the EORTC QLQ-C-30. Only those with available data at baseline and each time point are included.

The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. A change of at least 10 points on the standardized domain scores was required for it to be considered clinically meaningful.

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Global Health Status/QOL Domain at Weeks 12 and 24 Week 12	19.6 percentage of participants	22.1 percentage of participants
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Global Health Status/QOL Domain at Weeks 12 and 24 Week 24	14.9 percentage of participants	26.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days

Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.

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

Outcome measures

Measure	Placebo n=58 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=131 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Emotional Functioning Domain at Weeks 12 and 24 Week 12	25.0 percentage of participants	20.5 percentage of participants
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Emotional Functioning Domain at Weeks 12 and 24 Week 24	17.0 percentage of participants	21.7 percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.

Population: Safety population includes all participants who received at least 1 dose of study drug.

Hospitalizations due to adverse events exclude those for transfusions, elective procedures or protocol-driven procedures. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.

Outcome measures

Measure	Placebo n=79 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=160 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Related to Adverse Events Per Person Year	0.47 Hospitalizations per person-years Interval 0.3 to 0.75	0.77 Hospitalizations per person-years Interval 0.62 to 0.96

SECONDARY outcome

Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.

Population: Participants with at least one hospitalization.

Hospitalizations due to adverse events exclude those for transfusions, elective procedures or protocol-driven procedures. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.

Outcome measures

Measure	Placebo n=14 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=57 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Healthcare Resource Utilization (HRU): Duration of Hospitalizations Due to Adverse Events	9.0 Days Interval 1.0 to 66.0	11.0 Days Interval 1.0 to 76.0

SECONDARY outcome

Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.

Population: Safety population includes all participants who received at least 1 dose of study drug.

Hospitalizations due to adverse events exclude those for transfusions, elective procedures or protocol-driven procedures. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient

Outcome measures

Measure	Placebo n=79 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=160 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Healthcare Resource Utilization (HRU): Number of Days of Hospitalization Due to Adverse Events Per Person-Years	6.37 Days per person-years Interval 4.64 to 8.74	8.92 Days per person-years Interval 7.35 to 10.82

POST_HOC outcome

Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.

Population: Intent to treat population includes all participants who were randomized.

A participant was considered as having achieved an erythroid response when:

• a Hgb increase ≥1.5 g/dL compared to baseline and confirmed by another central laboratory hemoglobin value at 4 to 8 weeks after the first Hgb measurement that had also increased ≥1.5 g/dL for at least 8 weeks. All Hgb values during this time interval must have had a ≥ 1.5 g/dL increase (ie, no central laboratory Hgb increase during this timeframe can be less than a 1.5 g/dL) OR - had an absolute reduction of 4 RBC transfusion units over any consecutive 56 days period compared to the baseline transfusion burden.

The baseline transfusion burden is the number of units over the 112 days prior to randomization divided by 2. Only transfusions given for a pre-transfusion Hgb value of 9.5 g/dL or less may be used in this response assessment.

Outcome measures

Measure	Placebo n=79 Participants 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.	Lenalidomide n=160 Participants Lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min.
Percentage of Participants Who Achieved an Erythroid Response Based on Original IWG 2006 Criteria	20.3 percentage of participants	35.6 percentage of participants

Adverse Events

Placebo

Serious events: 16 serious events

Other events: 70 other events

Deaths: 43 deaths

Lenalidomide

Serious events: 62 serious events

Other events: 154 other events

Deaths: 94 deaths

Serious adverse events

Measure	Placebo n=79 participants at risk Participants received 3 placebo capsules by mouth QD for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent	Lenalidomide n=160 participants at risk Participants received lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression or intolerable side effects. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance between 40 and 60 mL/min.
Blood and lymphatic system disorders ANAEMIA	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	3.1% 5/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Blood and lymphatic system disorders HAEMOLYSIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Blood and lymphatic system disorders NEUTROPENIA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.9% 3/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Blood and lymphatic system disorders PANCYTOPENIA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Blood and lymphatic system disorders THROMBOCYTOPENIA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Cardiac disorders ATRIAL FIBRILLATION	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Cardiac disorders ATRIAL FLUTTER	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Cardiac disorders CARDIAC FAILURE	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.9% 3/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Cardiac disorders CARDIAC FAILURE CONGESTIVE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Cardiac disorders MYOCARDIAL INFARCTION	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.2% 2/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Cardiac disorders TACHYARRHYTHMIA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Eye disorders CATARACT	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Eye disorders ULCERATIVE KERATITIS	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders ABDOMINAL PAIN	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders ASCITES	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders CONSTIPATION	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders GASTRITIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders GASTROINTESTINAL NECROSIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders HAEMATEMESIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders INGUINAL HERNIA, OBSTRUCTIVE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders PANCREATITIS	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders PANCREATITIS NECROTISING	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders UPPER GASTROINTESTINAL HAEMORRHAGE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
General disorders DISUSE SYNDROME	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
General disorders GENERAL PHYSICAL HEALTH DETERIORATION	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.2% 2/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
General disorders MALAISE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
General disorders MULTI-ORGAN FAILURE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
General disorders PYREXIA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
General disorders SUDDEN DEATH	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Hepatobiliary disorders HEPATIC CIRRHOSIS	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Hepatobiliary disorders HEPATIC FAILURE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations ATYPICAL PNEUMONIA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations BRONCHITIS	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations BRONCHOPNEUMONIA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations BRONCHOPULMONARY ASPERGILLOSIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations CELLULITIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.2% 2/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations ESCHERICHIA SEPSIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations INFLUENZA	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations LOBAR PNEUMONIA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations LOWER RESPIRATORY TRACT INFECTION	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations NEUTROPENIC SEPSIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.9% 3/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations PNEUMONIA	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	6.2% 10/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations PNEUMONIA VIRAL	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations PSEUDOMONAL SEPSIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations STAPHYLOCOCCAL INFECTION	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations TOOTH ABSCESS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations URINARY TRACT INFECTION	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.2% 2/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Injury, poisoning and procedural complications FEMORAL NECK FRACTURE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Injury, poisoning and procedural complications FEMUR FRACTURE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.2% 2/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Injury, poisoning and procedural complications HIP FRACTURE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Injury, poisoning and procedural complications HUMERUS FRACTURE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Injury, poisoning and procedural complications SPINAL FRACTURE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Injury, poisoning and procedural complications THORACIC VERTEBRAL FRACTURE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Injury, poisoning and procedural complications TRAUMATIC INTRACRANIAL HAEMORRHAGE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.2% 2/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Metabolism and nutrition disorders DECREASED APPETITE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Metabolism and nutrition disorders HYPOKALAEMIA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Musculoskeletal and connective tissue disorders INTERVERTEBRAL DISC PROTRUSION	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Musculoskeletal and connective tissue disorders MYALGIA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Musculoskeletal and connective tissue disorders RHABDOMYOLYSIS	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ACUTE MYELOID LEUKAEMIA	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ADENOCARCINOMA OF COLON	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CHRONIC MYELOMONOCYTIC LEUKAEMIA	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) INVASIVE DUCTAL BREAST CARCINOMA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG SQUAMOUS CELL CARCINOMA STAGE IV	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MYELODYSPLASTIC SYNDROME	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.2% 2/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PROSTATE CANCER	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SQUAMOUS CELL CARCINOMA OF LUNG	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SQUAMOUS CELL CARCINOMA OF THE TONGUE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Nervous system disorders CEREBROVASCULAR ACCIDENT	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Nervous system disorders DIZZINESS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Nervous system disorders DYSKINESIA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Nervous system disorders TRANSIENT ISCHAEMIC ATTACK	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.2% 2/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Psychiatric disorders MENTAL STATUS CHANGES	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.2% 2/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Renal and urinary disorders NEPHROLITHIASIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Renal and urinary disorders RENAL COLIC	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Renal and urinary disorders RENAL FAILURE ACUTE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Respiratory, thoracic and mediastinal disorders ACUTE RESPIRATORY DISTRESS SYNDROME	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Respiratory, thoracic and mediastinal disorders ACUTE RESPIRATORY FAILURE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Respiratory, thoracic and mediastinal disorders ASTHMA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Respiratory, thoracic and mediastinal disorders LUNG DISORDER	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.9% 3/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Respiratory, thoracic and mediastinal disorders PULMONARY OEDEMA	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.00% 0/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Skin and subcutaneous tissue disorders NEURODERMATITIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Skin and subcutaneous tissue disorders SKIN ULCER	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.2% 2/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Vascular disorders CIRCULATORY COLLAPSE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Vascular disorders DEEP VEIN THROMBOSIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	1.9% 3/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.

Other adverse events

Measure	Placebo n=79 participants at risk Participants received 3 placebo capsules by mouth QD for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent	Lenalidomide n=160 participants at risk Participants received lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression or intolerable side effects. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance between 40 and 60 mL/min.
Blood and lymphatic system disorders ANAEMIA	5.1% 4/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	5.0% 8/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Blood and lymphatic system disorders LEUKOPENIA	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	13.8% 22/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Blood and lymphatic system disorders NEUTROPENIA	11.4% 9/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	63.7% 102/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Blood and lymphatic system disorders THROMBOCYTOPENIA	7.6% 6/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	41.2% 66/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Eye disorders CONJUNCTIVITIS	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	5.0% 8/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders ABDOMINAL PAIN	6.3% 5/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	6.2% 10/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	6.3% 5/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	7.5% 12/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders CONSTIPATION	11.4% 9/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	22.5% 36/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders DIARRHOEA	22.8% 18/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	43.1% 69/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders DYSPEPSIA	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	5.0% 8/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders NAUSEA	15.2% 12/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	11.9% 19/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Gastrointestinal disorders VOMITING	6.3% 5/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	8.1% 13/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
General disorders ASTHENIA	16.5% 13/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	23.8% 38/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
General disorders FATIGUE	11.4% 9/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	22.5% 36/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
General disorders OEDEMA PERIPHERAL	17.7% 14/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	21.9% 35/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
General disorders PYREXIA	7.6% 6/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	12.5% 20/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations INFLUENZA	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	6.2% 10/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations NASOPHARYNGITIS	11.4% 9/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	11.9% 19/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations PNEUMONIA	5.1% 4/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	2.5% 4/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	6.3% 5/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	2.5% 4/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Infections and infestations URINARY TRACT INFECTION	7.6% 6/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	5.6% 9/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Injury, poisoning and procedural complications OVERDOSE	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	9.4% 15/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Investigations ALANINE AMINOTRANSFERASE INCREASED	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	8.1% 13/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Investigations SERUM FERRITIN INCREASED	5.1% 4/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	0.62% 1/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Investigations WEIGHT DECREASED	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	10.6% 17/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Metabolism and nutrition disorders DECREASED APPETITE	3.8% 3/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	11.9% 19/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Metabolism and nutrition disorders HYPOKALAEMIA	0.00% 0/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	6.2% 10/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Metabolism and nutrition disorders IRON OVERLOAD	5.1% 4/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	2.5% 4/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Musculoskeletal and connective tissue disorders ARTHRALGIA	6.3% 5/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	8.8% 14/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Musculoskeletal and connective tissue disorders BACK PAIN	11.4% 9/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	10.0% 16/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	11.9% 19/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Musculoskeletal and connective tissue disorders MYALGIA	1.3% 1/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	5.0% 8/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	3.8% 3/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	11.2% 18/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Nervous system disorders DIZZINESS	11.4% 9/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	8.1% 13/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Nervous system disorders HEADACHE	10.1% 8/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	5.6% 9/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Psychiatric disorders INSOMNIA	8.9% 7/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	5.6% 9/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Respiratory, thoracic and mediastinal disorders COUGH	7.6% 6/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	10.6% 17/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	11.4% 9/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	9.4% 15/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	6.2% 10/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Skin and subcutaneous tissue disorders DRY SKIN	2.5% 2/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	7.5% 12/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Skin and subcutaneous tissue disorders NIGHT SWEATS	3.8% 3/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	5.0% 8/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Skin and subcutaneous tissue disorders PRURITUS	11.4% 9/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	18.8% 30/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.
Skin and subcutaneous tissue disorders RASH	5.1% 4/79 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.	21.9% 35/160 • From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group Second primary malignancies were monitored as events of interest and reported as serious adverse events for at least 5 years from randomization unless the participants withdrew consent from the study, died or were lost to follow-up.

Additional Information

Anne McClain, Senior Study Manager

Celgene Corporation

Phone: 888-260-1588

Email: clinicaltrialdisclosure@celgene.com

Results disclosure agreements

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