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

• ClinicalTrials.gov Identifier: NCT00405756
• Recruitment Status: Completed
• First Posted: November 30, 2006
• Results First Posted: May 11, 2012
• Last Update Posted: January 11, 2017
• Sponsor: Celgene Corporation
• Information provided by (Responsible Party): Celgene Corporation

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Newly Diagnosed Multiple Myeloma
• Interventions: Drug: Lenalidomide: Double-blind Induction; Drug: Melphalan; Drug: Prednisone; Drug: Aspirin; Drug: Placebo; Drug: Lenalidomide: Double-blind Maintenance; Drug: Lenalidomide: Open-label
• Enrollment: 459

Participant Flow

Recruitment Details	Data represents a May 11, 2010 data cut-off. The study is ongoing.
Pre-assignment Details	Of the 606 subjects screened for this study, 147 failed screening. Reasons for screen failures included: laboratory values not met (45 subjects); diagnostic criteria for measurable multiple myeloma not met (30 subjects); other inclusion/exclusion criteria not met (30 subjects); subject withdrawal of consent (14 subjects); and other (28 subjects).

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Period Title: Double-blind Treatment
Started	152 [1]	153	154
Safety Population	150 [2]	152	153
Completed	0 [3]	0	0
Not Completed	152	153	154
Reason Not Completed
Ongoing in Double-blind Treatment	45	24	18
Adverse Event	31	27	12
Disease Progression	47	81	102
Lack of Efficacy	1	4	2
Withdrawal by Subject	15	9	10
Lost to Follow-up	1	0	0
Death	4	4	4
Protocol Violation	1	0	2
Other	7	4	4
[1] Intent to treat population of all randomized participants; [2] Participants who took at least one dose of study drug.; [3] Double-blind Treatment Period had no defined completion.
Period Title: Open-label Extension
Started	19	47	72
Completed	0 [1]	0	0
Not Completed	19	47	72
Reason Not Completed
Ongoing in Open Label Period	7	15	25
Adverse Event	1	3	7
Disease Progression	8	23	26
Withdrawal by Subject	2	3	3
Death	1	2	4
Other	0	1	7
[1] Participants continue until disease progression or other reason for discontinuing.
Period Title: Follow-up
Started	75 [1]	90 [2]	88 [3]
Completed	0	0	0
Not Completed	75	90	88
Reason Not Completed
Ongoing in Follow-up Period	52	51	60
Death	21	31	24
Lost to Follow-up	2	8	4
[1] 66 participants from Double-blind and 9 from the Open Label Extension; [2] 65 participants from the Double-blind and 25 from the Open Label Extension; [3] 52 participants from the Double-blind and 36 from the Open Label Extension

Baseline Characteristics

Arm/Group Title		MPR+R	MPR+p	MPp+p	Total
Arm/Group Description		Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Total of all reporting groups
Overall Number of Baseline Participants		152	153	154	459
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	152 participants	153 participants	154 participants	459 participants
		72.0 (5.33)	72.1 (5.20)	72.0 (5.26)	72.0 (5.25)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	152 participants	153 participants	154 participants	459 participants
<=75 years		116	116	116	348
>75 years		36	37	38	111
Gender; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	152 participants	153 participants	154 participants	459 participants
	Female	81 53.3%	71 46.4%	79 51.3%	231 50.3%
	Male	71 46.7%	82 53.6%	75 48.7%	228 49.7%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	152 participants	153 participants	154 participants	459 participants
White		151	151	151	453
Black		1	0	0	1
Hispanic		0	0	1	1
Asian / Pacific Islander		0	0	0	0
American Indian or Alaska Native		0	0	0	0
Other		0	2	2	4
Weight; Mean (Standard Deviation); Unit of measure: Kilograms
	Number Analyzed	152 participants	153 participants	154 participants	459 participants
		73.5 (14.77)	72.0 (12.79)	72.1 (15.20)	72.5 (14.28)
Height; Mean (Standard Deviation); Unit of measure: Centimeter
	Number Analyzed	152 participants	153 participants	154 participants	459 participants
		164.8 (9.81)	165.3 (9.33)	165.7 (9.79)	165.3 (9.63)
Systolic Blood Pressure; Mean (Standard Deviation); Unit of measure: mmHg
	Number Analyzed	152 participants	153 participants	154 participants	459 participants
		133.9 (17.71)	135.5 (18.60)	136.4 (20.13)	135.3 (18.83)
Diastolic Blood Pressure; Mean (Standard Deviation); Unit of measure: mmHg
	Number Analyzed	152 participants	153 participants	154 participants	459 participants
		78.5 (9.53)	77.4 (9.99)	78.8 (10.40)	78.2 (9.98)
Temperature; Mean (Standard Deviation); Unit of measure: Degrees centigrade
	Number Analyzed	152 participants	153 participants	154 participants	459 participants
		36.5 (0.41)	36.5 (0.38)	36.5 (0.40)	36.5 (0.40)
Pulse; Mean (Standard Deviation); Unit of measure: Beats per minute
	Number Analyzed	152 participants	153 participants	154 participants	459 participants
		76.0 (9.77)	77.3 (10.50)	76.3 (10.80)	76.5 (10.36)
Karnofsky Performance Scale [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	152 participants	153 participants	154 participants	459 participants
		81.1 (11.95)	82.2 (11.71)	84.0 (11.46)	82.4 (11.74)
		[1] Measure Description: Karnofsky Performance Scale classifies patients according to their functional impairment. Scores range from 0-100, the lower the score, the greater the impairment and worse prospect of survival for most serious illnesses.
International Staging System (ISS) [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	152 participants	153 participants	154 participants	459 participants
Stage I		28	32	28	88
Stage II		50	47	48	145
Stage III		74	74	78	226
		[1] Measure Description: ISS form multiple myeloma divides myeloma into 3 stages based only on the serum beta-2 microglobulin and serum albumin levels. Higher stages represent more advanced disease.
Creatinine clearance; Measure Type: Number; Unit of measure: Participants	Number Analyzed	152 participants	153 participants	154 participants	459 participants
>=60 ml/min		72	83	77	232
<60 ml/min		78	69	76	223
Missing		2	1	1	4
Beta2 Microglobulin; Measure Type: Number; Unit of measure: Participants	Number Analyzed	152 participants	153 participants	154 participants	459 participants
>5.5 mg/L		74	78	67	219
<=5.5 mg/L		77	75	87	239
Missing		1	0	0	1
Albumin; Measure Type: Number; Unit of measure: Participants	Number Analyzed	152 participants	153 participants	154 participants	459 participants
>35 g/L		87	82	81	250
<= 35 g/L		63	70	72	205
Missing		2	1	1	4
C-reactive Protein; Measure Type: Number; Unit of measure: Participants	Number Analyzed	152 participants	153 participants	154 participants	459 participants
>4 mg/L		65	56	64	185
<=4 mg/L		84	94	89	267
Missing		3	3	1	7
Multiple Myeloma Subtype; Measure Type: Number; Unit of measure: Participants	Number Analyzed	152 participants	153 participants	154 participants	459 participants
Immunoglobulin A (IgA)		39	38	33	110
Other		108	112	116	336
Missing		5	3	5	13
Plasma Cells in the Bone Marrow; Mean (Standard Deviation); Unit of measure: Percentage of plasma cells
	Number Analyzed	152 participants	153 participants	154 participants	459 participants
		39.8 (24.79)	39.3 (25.01)	37.9 (23.65)	39.0 (24.45)

Outcome Measures

1. Primary Outcome

Title	Kaplan Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Central Adjudication Committee (CAC)
Description	Data as of 11 May 2010 cutoff. PFS was calculated as the time from randomization to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.
Time Frame	up to 165 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Median (95% Confidence Interval); Unit of Measure: weeks
	136.1 [1]; (86.14 to NA)	62.1; (56.14 to 72.14)	56.1; (52.14 to 68.14)

[1]

Upper limit not estimable because of the number of participants without progressive disease at data cut-off.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPp+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.395
	Confidence Interval	(2-Sided) 95%; 0.278 to 0.560
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.494
	Confidence Interval	(2-Sided) 95%; 0.347 to 0.702
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MPR+p, MPp+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.134
	Comments	The p-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.796
	Confidence Interval	(2-Sided) 95%; 0.589 to 1.075
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Kaplan Meier Estimates of Progression-free Survival (PFS) From Start of Maintenance Therapy Period Based on the Response Assessment by the Central Adjudication Committee (CAC)
Description	Data as of 11 May 2010 cutoff. PFS calculated from the start of the Maintenance period to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.
Time Frame	Approximately week 37 (start of cycle 10) to week 165

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MPR+R	MPR+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	88	94
Median (95% Confidence Interval); Unit of Measure: weeks
	112.0 [1]; (83.29 to NA)	32.3; (23.57 to 52.14)

[1]

Upper limit not estimable because of the number of participants without progressive disease at data cut-off.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	P-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.340
	Confidence Interval	(2-Sided) 95%; 0.214 to 0.541
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Kaplan Meier Estimates of Overall Survival (OS)
Description	Data as of 11 May 2010 cutoff. Overall survival (OS) was defined as the time between randomization and death. Participants who died, regardless of the cause of death, were considered to have had an event. Participants who were lost to follow-up prior to the end of the trial, or who were withdrawn from the trial, were censored at the time of last contact. Participants who were still being treated were censored at the last available date available, or clinical cut-off date, if it was earlier.
Time Frame	up to 177 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Median (95% Confidence Interval); Unit of Measure: weeks
	NA [1]; (NA to NA)	NA [1]; (148.43 to NA)	NA [1]; (NA to NA)

[1]

Not able to estimate since few participants died as of the May 11, 2010 cut-off.

4. Secondary Outcome

Title	Kaplan Meier Estimates of Time to Progression (TTP) Based on the Response Assessment by the Central Adjudication Committee (CAC)
Description	Data as of 11 May 2010 cutoff. TTP was the time between randomization and disease progression as determined by the CAC. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.
Time Frame	up to 165 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Median (95% Confidence Interval); Unit of Measure: weeks
	148.1 [1]; (100.00 to NA)	62.7; (57.14 to 74.14)	61.3; (52.29 to 70.14)

[1]

Upper limit not estimable because of the number of participants without progressive disease at data cut-off.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPp+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.337
	Confidence Interval	(2-Sided) 95%; 0.231 to 0.493
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.414
	Confidence Interval	(2-Sided) 95%; 0.284 to 0.603
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MPR+p, MPp+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.223
	Comments	The p-value is based on unstratified log rank test of Kaplan-Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.826
	Confidence Interval	(2-Sided) 95%; 0.606 to 1.125
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period
Description	Data as of 11 May 2010 cutoff. Best response was determined by the Central Assessment Committee (CAC) based on the European Group for Blood and Marrow Transplantation (EBMT) criteria: Complete Response (CR)-absence of serum and urine monoclonal paraprotein for 6 weeks, plus no increase in size or number of bone lesions, plus other factors); Partial Response (PR)-not all CR criteria, plus >=50% reduction in serum monoclonal paraprotein plus others; Stable Disease (SD)- not PR or PD; Progressive Disease (PD)- reappearance of monoclonal paraprotein, bone lesions, other; Not Evaluable (NE).
Time Frame	Up to 165 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Measure Type: Number; Unit of Measure: participants
Complete response (CR)	15	5	5
Partial response (PR)	102	99	72
Stable disease (SD)	28	40	70
Progressive disease (PD)	0	2	0
Response not evaluable (NE)	7	7	7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPp+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value calculation excludes the category - Response not evaluable (NE)
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.009
	Comments	P-value calculation excludes the category - Response not evaluable (NE)
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MPR+p, MPp+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.003
	Comments	P-value calculation excludes the category - Response not evaluable (NE)
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPp+p
	Comments	Based on dichotomized response: 1) CR or PR 2) SD or PD or NE
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.34
	Confidence Interval	(2-Sided) 95%; 2.04 to 5.47
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments	Based on dichotomized response: 1) CR or PR 2) SD or PD or NE
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.096
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.58
	Confidence Interval	(2-Sided) 95%; 0.95 to 2.62
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	MPR+p, MPp+p
	Comments	Based on dichotomized response: 1) CR or PR 2) SD or PD or NE
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.12
	Confidence Interval	(2-Sided) 95%; 1.33 to 3.37
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Time to First Response
Description	Data as of 11 May 2010 cutoff. Time to first response was defined as the time from start of treatment until first response as assessed by the Central Assessment Committee (CMC) based on European Group for Blood and Marrow Transplantation (EBMT) criteria.
Time Frame	Up to 66 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	117	104	77
Mean (Standard Deviation); Unit of Measure: weeks
	10.0 (7.40)	9.3 (6.55)	16.2 (11.59)

7. Secondary Outcome

Title	Kaplan Meier Estimates for Duration of Response as Determined by the Central Adjudication Committee (CAC)
Description	Data as of 11 May 2010 cutoff. Duration of myeloma response was defined as the time from the initial response date to the earlier of progressive disease (PD) as determined by the CAC or death on study. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria. PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.
Time Frame	Up to 149 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	117	104	77
Median (95% Confidence Interval); Unit of Measure: weeks
	121.6 [1]; (96.00 to NA)	56.1; (52.14 to 64.29)	55.4; (44.14 to 76.14)

[1]

Upper limit not estimable because of the number of participants without progressive disease at data cut-off.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPp+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.348
	Confidence Interval	(2-Sided) 95%; 0.228 to 0.531
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.419
	Confidence Interval	(2-Sided) 95%; 0.281 to 0.623
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MPR+p, MPp+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.302
	Comments	The p-value is based on unstratified log rank test of Kaplan Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.825
	Confidence Interval	(2-Sided) 95%; 0.571 to 1.191
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Kaplan Meier Estimates for Time to Next Antimyeloma Therapy
Description	Data as of 11 May 2010 cutoff. Time to the next antimyeloma therapy was defined as time from randomization to the start of another non-protocol antimyeloma therapy. Participants who do not receive another anti-myeloma therapy were censored at the last assessment or follow-up visit known to have received no new therapy.
Time Frame	Up to 168 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Median (95% Confidence Interval); Unit of Measure: weeks
	128.9 [1]; (99.86 to NA)	66.1; (60.14 to 76.00)	66.3; (61.14 to 72.43)

[1]

Upper limit not estimable because of the number of participants who had not started a non-protocol anti-myeloma therapy at data cut-off.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPp+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.404
	Confidence Interval	(2-Sided) 95%; 0.296 to 0.553
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MPR+R, MPR+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The p-value is based on unstratified log rank test of Kaplan Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.499
	Confidence Interval	(2-Sided) 95%; 0.363 to 0.688
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MPR+p, MPp+p
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.169
	Comments	The p-value is based on unstratified log rank test of Kaplan Meier curve differences between the treatment groups.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.827
	Confidence Interval	(2-Sided) 95%; 0.630 to 1.085
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period
Description	Data as of 11 May 2010 cutoff. Participant counts in different categories of TEAEs during the double-blind treatment period. A TEAE is as any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE. Dose reduction includes reduction with or without interruption.
Time Frame	Up to 169 weeks (Double-blind therapy period plus 4 weeks)

Outcome Measure Data

Analysis Population Description

Safety population

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

10. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLC-C30 is a 30-item questionnaire to assess the quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); two used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better quality of life.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=114,121,125)	2.3 (26.13)	5.6 (18.86)	6.1 (19.41)
Cycle 7 - approximately Month 7 (n=96,108,110)	8.0 (24.95)	8.1 (22.48)	4.2 (23.92)
Cycle 10 - approximately Month 10 (n=84,86,96)	12.4 (25.33)	8.8 (24.70)	6.2 (24.60)
Cycle 13 - approximately Month 13 (n=70,70,82)	7.6 (28.32)	8.8 (24.02)	5.4 (22.80)
Cycle 16 - approximately Month 16 (n=61,50,62)	10.7 (25.28)	7.2 (26.29)	8.1 (25.11)

11. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=120,127,130)	1.9 (23.72)	3.3 (21.64)	4.5 (18.68)
Cycle 7 - approximately Month 7 (n=100,112,112)	8.2 (22.71)	8.1 (20.54)	2.7 (23.20)
Cycle 10 - approximately Month 10 (n=88,95,96)	8.9 (22.75)	8.5 (25.62)	5.1 (20.42)
Cycle 13 - approximately Month 13 (n=75,74,83)	8.6 (24.04)	9.7 (25.39)	3.3 (20.30)
Cycle 16 - approximately Month 16 (n=64,53,63)	10.0 (25.00)	7.6 (22.66)	1.1 (19.30)

12. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of role functioning.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=119,127,130)	1.8 (33.18)	3.0 (30.75)	7.4 (26.34)
Cycle 7 - approximately Month 7 (n=99,112,113)	5.7 (35.57)	8.0 (32.42)	6.9 (31.16)
Cycle 10 - approximately Month 10 (n=86,95,95)	9.3 (35.76)	7.5 (36.29)	5.6 (31.29)
Cycle 13 - approximately Month 13 (n=74,74,82)	9.7 (40.36)	11.7 (33.42)	5.7 (30.68)
Cycle 16 - approximately Month 16 (n=64,53,63)	12.2 (40.09)	8.5 (34.22)	7.1 (31.93)

13. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of emotional functioning.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=115,125,128)	4.8 (25.00)	2.7 (22.59)	6.8 (18.75)
Cycle 7 - approximately Month 7 (n=98,111,112)	8.8 (24.94)	4.2 (20.38)	5.0 (21.56)
Cycle 10 - approximately Month 10 (n=86,92,97)	9.0 (23.28)	1.6 (22.07)	4.7 (22.05)
Cycle 13 - approximately Month 13 (n=73,73,83)	8.2 (24.59)	1.1 (21.78)	6.6 (21.78)
Cycle 16 - approximately Month 16 (n=63,52,63)	9.9 (23.23)	-0.2 (21.57)	6.9 (19.72)

14. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of cognitive functioning.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=115,125,128)	0.3 (21.51)	-2.0 (21.33)	1.3 (16.68)
Cycle 7 - approximately Month 7 (n=98,111,113)	2.9 (22.31)	0.1 (17.33)	0.7 (18.42)
Cycle 10 - approximately Month 10 (n=87,92,97)	1.0 (22.64)	-4.4 (19.89)	-2.7 (20.65)
Cycle 13 - approximately Month 13 (n=73,73,83)	-0.0 (21.34)	-3.0 (23.78)	-1.4 (17.69)
Cycle 16 - approximately Month 16 (n=63,52,63)	0.3 (22.29)	-3.5 (27.48)	-4.0 (18.13)

15. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of social functioning.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=115,125,127)	5.1 (35.05)	0.3 (26.60)	6.0 (22.78)
Cycle 7 - approximately Month 7 (n=98,111,112)	8.3 (33.87)	4.4 (24.48)	6.1 (26.57)
Cycle 10 - approximately Month 10 (n=87,92,97)	10.9 (34.27)	4.5 (29.87)	4.1 (27.22)
Cycle 13 - approximately Month 13 (n=72,73,83)	11.8 (32.91)	7.5 (29.80)	6.2 (27.63)
Cycle 16 - approximately Month 16 (n=63,52,63)	13.2 (33.35)	6.1 (30.79)	9.8 (28.66)

16. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the fatigue scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=120,127,129)	-3.0 (25.61)	-5.5 (24.08)	-5.1 (24.33)
Cycle 7 - approximately Month 7 (n=100,112,110)	-7.6 (23.00)	-9.5 (25.97)	-5.7 (27.32)
Cycle 10 - approximately Month 10 (n=87,95,95)	-7.5 (27.31)	-7.5 (29.78)	-6.9 (28.31)
Cycle 13 - approximately Month 13 (n=74,74,82)	-7.1 (26.08)	-10.7 (30.33)	-7.5 (27.29)
Cycle 16 - approximately Month 16 (n=64,53,62)	-10.0 (26.86)	-9.7 (28.77)	-4.1 (26.34)

17. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the nausea/vomiting scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=120,127,130)	3.3 (19.40)	-1.3 (17.14)	-0.0 (17.36)
Cycle 7 - approximately Month 7 (n=99,112,112)	0.5 (14.57)	-0.7 (19.94)	0.7 (14.73)
Cycle 10 - approximately Month 10 (n=87,95,97)	1.9 (16.75)	-1.4 (19.40)	0.3 (14.23)
Cycle 13 - approximately Month 13 (n=75,72,83)	0.7 (13.55)	-3.0 (19.65)	-0.4 (12.48)
Cycle 16 - approximately Month 16 (n=64,52,62)	1.0 (12.90)	-4.2 (18.65)	-1.3 (9.21)

18. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the pain scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=120,127,129)	-14.4 (32.76)	-13.8 (33.60)	-13.4 (29.32)
Cycle 7 - approximately Month 7 (n=100,112,113)	-17.8 (36.18)	-16.5 (33.45)	-11.5 (33.49)
Cycle 10 - approximately Month 10 (n=88,95,97)	-17.2 (34.78)	-15.6 (35.30)	-9.8 (31.71)
Cycle 13 - approximately Month 13 (n=74,74,83)	-13.7 (40.48)	-14.9 (33.28)	-12.1 (27.46)
Cycle 16 - approximately Month 16 (n=64,53,63)	-20.3 (33.92)	-11.0 (33.00)	-12.2 (29.96)

19. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the dyspnoea scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=117,126,126)	-2.6 (29.74)	-6.4 (32.04)	-0.0 (23.48)
Cycle 7 - approximately Month 7 (n=100,110,110)	-1.7 (28.18)	-8.5 (32.07)	2.1 (20.82)
Cycle 10 - approximately Month 10 (n=86,93,96)	-4.3 (30.60)	-4.3 (35.87)	3.8 (25.07)
Cycle 13 - approximately Month 13 (n=73,73,81)	-5.0 (30.26)	-2.3 (30.60)	-0.0 (22.35)
Cycle 16 - approximately Month 16 (n=62,53,62)	-3.2 (29.39)	-6.3 (32.07)	1.6 (22.92)

20. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the insomnia scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=118,124,128)	2.0 (33.56)	-1.6 (31.77)	-5.0 (27.77)
Cycle 7 - approximately Month 7 (n=100,109,111)	-1.0 (29.76)	-6.4 (27.02)	-5.7 (32.06)
Cycle 10 - approximately Month 10 (n=87,94,96)	-5.0 (28.99)	-2.5 (25.04)	-1.7 (32.58)
Cycle 13 - approximately Month 13 (n=75,73,83)	-4.9 (29.86)	0.9 (29.38)	-6.8 (29.80)
Cycle 16 - approximately Month 16 (n=64,53,63)	-4.7 (32.46)	-0.6 (32.36)	-3.7 (31.18)

21. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the appetite loss scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=119,125,130)	1.7 (36.54)	1.9 (34.73)	-5.6 (25.96)
Cycle 7 - approximately Month 7 (n=99,111,111)	-3.7 (33.64)	-5.7 (31.75)	-5.7 (27.66)
Cycle 10 - approximately Month 10 (n=87,93,96)	-5.0 (33.15)	-5.4 (29.20)	-8.0 (29.32)
Cycle 13 - approximately Month 13 (n=75,72,83)	-6.2 (36.23)	-8.8 (30.13)	-4.8 (32.15)
Cycle 16 - approximately Month 16 (n=64,52,63)	-7.8 (36.01)	-16.0 (35.24)	-6.4 (28.62)

22. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the constipation scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=114,124,128)	-1.8 (34.31)	4.8 (30.86)	-4.9 (27.45)
Cycle 7 - approximately Month 7 (n=96,111,112)	-3.5 (36.35)	0.6 (30.14)	-2.7 (31.05)
Cycle 10 - approximately Month 10 (n=86,93,97)	-5.0 (34.88)	-1.1 (28.43)	-1.7 (26.95)
Cycle 13 - approximately Month 13 (n=73,73,81)	-5.0 (31.27)	-2.7 (28.74)	-3.3 (29.16)
Cycle 16 - approximately Month 16 (n=63,51,62)	-1.6 (31.36)	-5.2 (30.82)	-2.2 (32.44)

23. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the diarrhea scale = higher level of symptomatology/problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=115,125,124)	2.3 (28.85)	1.9 (24.06)	3.2 (25.65)
Cycle 7 - approximately Month 7 (n=98,109,112)	3.4 (25.54)	-1.2 (23.09)	0.9 (22.13)
Cycle 10 - approximately Month 10 (n=87,92,95)	1.1 (22.98)	1.4 (20.91)	-0.0 (21.19)
Cycle 13 - approximately Month 13 (n=73,73,80)	5.5 (30.43)	-1.4 (18.78)	0.8 (18.35)
Cycle 16 - approximately Month 16 (n=63,52,61)	10.6 (35.83)	1.3 (19.75)	0.5 (17.74)

24. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a problem scale like the financial problems scale = higher level of financial problems.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=111,123,125)	2.4 (24.91)	-1.1 (19.06)	-2.9 (18.93)
Cycle 7 - approximately Month 7 (n=94,111,112)	2.1 (23.85)	-0.6 (28.07)	-2.1 (22.50)
Cycle 10 - approximately Month 10 (n=84,92,97)	6.0 (21.44)	0.7 (28.81)	-1.7 (19.47)
Cycle 13 - approximately Month 13 (n=70,72,83)	4.8 (21.45)	-0.5 (28.80)	-4.0 (26.75)
Cycle 16 - approximately Month 16 (n=61,52,63)	1.6 (20.58)	-0.6 (35.24)	-5.3 (30.06)

25. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the disease symptoms scale = higher level of symptomatology.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=113,121,127)	-8.9 (19.56)	-8.7 (19.13)	-5.4 (15.83)
Cycle 7 - approximately Month 7 (n=96,109,112)	-9.0 (20.64)	-9.7 (23.25)	-6.0 (20.81)
Cycle 10 - approximately Month 10 (n=85,91,95)	-7.9 (23.00)	-7.1 (23.85)	-5.4 (18.79)
Cycle 13 - approximately Month 13 (n=72,73,82)	-7.2 (25.91)	-8.8 (24.90)	-6.3 (21.84)
Cycle 16 - approximately Month 16 (n=62,51,62)	-10.5 (23.87)	-5.9 (25.79)	-3.3 (20.67)

26. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the side effects scale = higher level of symptomatology.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=113,120,125)	1.3 (13.37)	0.1 (13.28)	0.6 (12.67)
Cycle 7 - approximately Month 7 (n=95,108,111)	0.4 (15.22)	-1.7 (14.27)	1.8 (12.94)
Cycle 10 - approximately Month 10 (n=85,89,94)	-1.6 (14.46)	0.0 (15.99)	0.3 (12.61)
Cycle 13 - approximately Month 13 (n=72,72,81)	-3.8 (15.61)	-1.0 (14.59)	0.3 (12.60)
Cycle 16 - approximately Month 16 (n=62,50,61)	-2.1 (14.95)	-2.9 (14.16)	-0.9 (12.23)

27. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the future perspective scale, higher score = better perspective of the future.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=112,121,124)	4.7 (23.74)	4.3 (23.56)	7.6 (22.38)
Cycle 7 - approximately Month 7 (n=93,108,112)	14.6 (24.45)	7.7 (23.86)	9.8 (20.62)
Cycle 10 - approximately Month 10 (n=83,88,97)	17.3 (27.84)	6.6 (22.40)	14.5 (21.73)
Cycle 13 - approximately Month 13 (n=71,73,81)	17.3 (27.15)	6.3 (23.78)	11.9 (24.67)
Cycle 16 - approximately Month 16 (n=62,52,62)	18.5 (25.30)	7.7 (28.49)	14.4 (26.62)

28. Secondary Outcome

Title	Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale
Description	Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the body image scale, higher scores = better body image.
Time Frame	Baseline (Day 0), Months 4, 7, 10, 13, 16

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	MPR+R	MPR+p	MPp+p
Arm/Group Description:	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.	Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
Overall Number of Participants Analyzed	152	153	154
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 4 - approximately Month 4 (n=110,117,119)	2.1 (35.36)	-0.3 (37.27)	4.5 (25.65)
Cycle 7 - approximately Month 7 (n=88,104,108)	3.8 (33.32)	2.6 (37.94)	5.2 (27.78)
Cycle 10 - approximately Month 10 (n=79,83,94)	7.6 (33.32)	-4.0 (43.69)	3.9 (26.72)
Cycle 13 - approximately Month 13 (n=68,72,79)	1.0 (31.01)	-0.5 (44.23)	5.1 (32.51)
Cycle 16 - approximately Month 16 (n=59,52,61)	3.4 (32.58)	6.4 (41.25)	2.7 (28.08)

Adverse Events

Time Frame	Up to 169 weeks (Double-blind therapy period plus 4 weeks)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	MPR+R		MPR+p		MPp+p
Arm/Group Description	Double-blind induction therapy with melphalan/prednisone and lenalidomide 10 mg (MPR) for up to 9 cycles, followed by maintenance therapy with single-agent lenalidomide (R) 10mg from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.		Double-blind induction therapy with melphalan/prednisone and lenalidomide 10mg (MPR) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.		Double-blind induction therapy with melphalan/prednisone and placebo (MPp) for up to 9 cycles, followed by maintenance therapy with placebo (p) from cycle 10 to disease progression. Optional open-label extension therapy with lenalidomide up to 25 mg for participants with progressive disease.
All-Cause Mortality
	MPR+R		MPR+p		MPp+p
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	MPR+R		MPR+p		MPp+p
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/150 (44.00%)		62/152 (40.79%)		56/153 (36.60%)
Blood and lymphatic system disorders
Anaemia † 1	5/150 (3.33%)	5	8/152 (5.26%)	10	2/153 (1.31%)	2
Febrile neutropenia † 1	9/150 (6.00%)	9	2/152 (1.32%)	2	0/153 (0.00%)	0
Neutropenia † 1	6/150 (4.00%)	6	4/152 (2.63%)	5	1/153 (0.65%)	1
Thrombocytopenia † 1	2/150 (1.33%)	2	4/152 (2.63%)	4	1/153 (0.65%)	1
Pancytopenia † 1	1/150 (0.67%)	1	2/152 (1.32%)	2	1/153 (0.65%)	1
Leukopenia † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	1/153 (0.65%)	1
Haemolytic anaemia † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Cardiac disorders
Atrial fibrillation † 1	1/150 (0.67%)	1	3/152 (1.97%)	3	5/153 (3.27%)	6
Angina pectoris † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	2/153 (1.31%)	3
Bradycardia † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	2/153 (1.31%)	2
Cardiac failure † 1	2/150 (1.33%)	2	0/152 (0.00%)	0	1/153 (0.65%)	1
Cardiogenic shock † 1	2/150 (1.33%)	2	0/152 (0.00%)	0	1/153 (0.65%)	1
Palpitations † 1	2/150 (1.33%)	3	1/152 (0.66%)	2	0/153 (0.00%)	0
Coronary artery disease † 1	1/150 (0.67%)	1	1/152 (0.66%)	1	0/153 (0.00%)	0
Myocardial ischaemia † 1	2/150 (1.33%)	2	0/152 (0.00%)	0	0/153 (0.00%)	0
Acute coronary syndrome † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Acute myocardial infarction † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Atrial flutter † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Cardiac arrest † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Cardiac disorder † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Coronary artery occlusion † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Right ventricular failure † 1	0/150 (0.00%)	0	1/152 (0.66%)	2	0/153 (0.00%)	0
Sinus tachycardia † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Tachyarrhythmia † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Ear and labyrinth disorders
Vertigo † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Eye disorders
Cataract † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Retinal detachment † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Gastrointestinal disorders
Vomiting † 1	4/150 (2.67%)	5	1/152 (0.66%)	1	3/153 (1.96%)	3
Nausea † 1	3/150 (2.00%)	3	2/152 (1.32%)	2	2/153 (1.31%)	2
Constipation † 1	2/150 (1.33%)	2	3/152 (1.97%)	3	1/153 (0.65%)	1
Diarrhoea † 1	3/150 (2.00%)	3	1/152 (0.66%)	1	1/153 (0.65%)	2
Colitis † 1	1/150 (0.67%)	1	1/152 (0.66%)	1	0/153 (0.00%)	0
Inguinal hernia † 1	2/150 (1.33%)	2	0/152 (0.00%)	0	0/153 (0.00%)	0
Abdominal strangulated hernia † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Dysphagia † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Gastritis haemorrhagic † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Gastrointestinal haemorrhage † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Gastrointestinal obstruction † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Haemorrhoidal haemorrhage † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Ileus † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Melaena † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Pancreatic mass † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
General disorders
Pyrexia † 1	6/150 (4.00%)	6	2/152 (1.32%)	2	7/153 (4.58%)	8
Fatigue † 1	4/150 (2.67%)	4	2/152 (1.32%)	2	1/153 (0.65%)	1
General physical health deterioration † 1	2/150 (1.33%)	2	1/152 (0.66%)	1	2/153 (1.31%)	2
Asthenia † 1	0/150 (0.00%)	0	2/152 (1.32%)	2	1/153 (0.65%)	1
Oedema peripheral † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	2/153 (1.31%)	2
Chest pain † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Face oedema † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Malaise † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Pain † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Systemic inflammatory response syndrome † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Hepatobiliary disorders
Biliary colic † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Cholestasis † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Hepatitis toxic † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Immune system disorders
Hypersensitivity † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Infections and infestations
Pneumonia † 1	4/150 (2.67%)	5	8/152 (5.26%)	9	8/153 (5.23%)	8
Sepsis † 1	1/150 (0.67%)	1	3/152 (1.97%)	3	1/153 (0.65%)	1
Urinary tract infection † 1	2/150 (1.33%)	2	0/152 (0.00%)	0	3/153 (1.96%)	3
Bronchitis † 1	1/150 (0.67%)	1	2/152 (1.32%)	2	0/153 (0.00%)	0
Lower respiratory tract infection † 1	2/150 (1.33%)	2	0/152 (0.00%)	0	1/153 (0.65%)	1
Bronchopneumonia † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	1/153 (0.65%)	1
Cellulitis † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	1/153 (0.65%)	1
Cystitis † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	1/153 (0.65%)	1
Diverticulitis † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	1/153 (0.65%)	1
Herpes zoster † 1	1/150 (0.67%)	1	1/152 (0.66%)	1	0/153 (0.00%)	0
Infection † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	1/153 (0.65%)	1
Septic shock † 1	1/150 (0.67%)	1	1/152 (0.66%)	1	0/153 (0.00%)	0
Sinusitis † 1	2/150 (1.33%)	2	0/152 (0.00%)	0	0/153 (0.00%)	0
Upper respiratory tract infection † 1	2/150 (1.33%)	2	0/152 (0.00%)	0	0/153 (0.00%)	0
Appendicitis † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Arthritis infective † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Bronchitis bacterial † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Campylobacter infection † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Clostridium colitis † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Erysipelas † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Escherichia infection † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Escherichia sepsis † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Gastroenteritis † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Gastroenteritis Norwalk virus † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Herpes simplex † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Lobar pneumonia † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Meningitis † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Oral candidiasis † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Post procedural infection † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Pseudomembranous colitis † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Pyelonephritis chronic † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Streptococcal bacteraemia † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Streptococcal sepsis † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Viral upper respiratory tract infection † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Injury, poisoning and procedural complications
Accidental overdose † 1	1/150 (0.67%)	1	1/152 (0.66%)	1	0/153 (0.00%)	0
Femur fracture † 1	0/150 (0.00%)	0	2/152 (1.32%)	2	0/153 (0.00%)	0
Sternal fracture † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	2/153 (1.31%)	2
Thoracic vertebral fracture † 1	1/150 (0.67%)	1	1/152 (0.66%)	1	0/153 (0.00%)	0
Femoral neck fracture † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Hip fracture † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Humerus fracture † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Spinal compression fracture † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Spinal fracture † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Tendon rupture † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Therapeutic agent toxicity † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Traumatic fracture † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Fall † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	2/153 (1.31%)	2
Investigations
Monoclonal immunoglobulin present † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Metabolism and nutrition disorders
Dehydration † 1	2/150 (1.33%)	2	1/152 (0.66%)	1	0/153 (0.00%)	0
Hypercalcaemia † 1	2/150 (1.33%)	2	1/152 (0.66%)	1	0/153 (0.00%)	0
Hypocalcaemia † 1	2/150 (1.33%)	2	1/152 (0.66%)	1	0/153 (0.00%)	0
Hypokalaemia † 1	2/150 (1.33%)	2	1/152 (0.66%)	1	0/153 (0.00%)	0
Anorexia † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Diabetes mellitus † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Hyperglycaemia † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Hyperkalaemia † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Oral intake reduced † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Musculoskeletal and connective tissue disorders
Bone pain † 1	3/150 (2.00%)	3	2/152 (1.32%)	2	6/153 (3.92%)	7
Back pain † 1	2/150 (1.33%)	3	1/152 (0.66%)	1	1/153 (0.65%)	1
Arthralgia † 1	1/150 (0.67%)	1	2/152 (1.32%)	2	0/153 (0.00%)	0
Musculoskeletal pain † 1	2/150 (1.33%)	2	0/152 (0.00%)	0	1/153 (0.65%)	1
Arthropathy † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Bone lesion † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Gouty arthritis † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Intervertebral disc disorder † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Muscle haemorrhage † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Myositis † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Osteoarthritis † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Pain in extremity † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma † 1	0/150 (0.00%)	0	2/152 (1.32%)	2	2/153 (1.31%)	2
Leukaemia plasmacytic † 1	0/150 (0.00%)	0	2/152 (1.32%)	2	1/153 (0.65%)	2
Acute myeloid leukaemia † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Bowen's disease † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Breast cancer † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Bronchial carcinoma † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Light chain disease † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Lung neoplasm malignant † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Myelodysplastic syndrome † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Plasmacytoma † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Nervous system disorders
Syncope † 1	0/150 (0.00%)	0	2/152 (1.32%)	2	1/153 (0.65%)	1
Cerebral ischaemia † 1	1/150 (0.67%)	1	1/152 (0.66%)	1	0/153 (0.00%)	0
Dizziness † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	1/153 (0.65%)	1
Aphasia † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Cerebral haemorrhage † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Cognitive disorder † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Convulsion † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Hemiparesis † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Metabolic encephalopathy † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Neuralgia † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Neuropathy peripheral † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Nystagmus † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Parkinson's disease † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Presyncope † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Syncope vasovagal † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Transient ischaemic attack † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Psychiatric disorders
Depression † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Insomnia † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Psychotic disorder due to a general medical condition † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Renal and urinary disorders
Renal failure acute † 1	1/150 (0.67%)	1	2/152 (1.32%)	2	4/153 (2.61%)	4
Renal failure † 1	0/150 (0.00%)	0	3/152 (1.97%)	4	2/153 (1.31%)	2
Dysuria † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Nephrotic syndrome † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	2
Renal amyloidosis † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Urinary retention † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	2/153 (1.31%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	2/150 (1.33%)	3	3/152 (1.97%)	3	2/153 (1.31%)	2
Pulmonary embolism † 1	2/150 (1.33%)	2	3/152 (1.97%)	4	0/153 (0.00%)	0
Pleural effusion † 1	0/150 (0.00%)	0	2/152 (1.32%)	3	1/153 (0.65%)	1
Respiratory failure † 1	1/150 (0.67%)	1	1/152 (0.66%)	1	0/153 (0.00%)	0
Acute pulmonary oedema † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Bronchospasm † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Productive cough † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Pulmonary haemorrhage † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Skin and subcutaneous tissue disorders
Rash † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	1/153 (0.65%)	1
Blister † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Dermatitis exfoliative † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Drug eruption † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Erythema † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Vascular disorders
Deep vein thrombosis † 1	1/150 (0.67%)	1	6/152 (3.95%)	7	0/153 (0.00%)	0
Hypertension † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	2/153 (1.31%)	2
Thrombosis † 1	2/150 (1.33%)	2	1/152 (0.66%)	1	0/153 (0.00%)	0
Hypotension † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	1/153 (0.65%)	1
Aortic dissection † 1	0/150 (0.00%)	0	0/152 (0.00%)	0	1/153 (0.65%)	1
Peripheral ischaemia † 1	1/150 (0.67%)	1	0/152 (0.00%)	0	0/153 (0.00%)	0
Vasculitis † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
Venous thrombosis † 1	0/150 (0.00%)	0	1/152 (0.66%)	1	0/153 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (10.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	MPR+R		MPR+p		MPp+p
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	149/150 (99.33%)		151/152 (99.34%)		152/153 (99.35%)
Blood and lymphatic system disorders
Neutropenia † 1	117/150 (78.00%)	951	116/152 (76.32%)	807	78/153 (50.98%)	398
Anaemia † 1	99/150 (66.00%)	417	91/152 (59.87%)	351	82/153 (53.59%)	293
Thrombocytopenia † 1	103/150 (68.67%)	514	100/152 (65.79%)	532	68/153 (44.44%)	268
Leukopenia † 1	54/150 (36.00%)	418	58/152 (38.16%)	449	49/153 (32.03%)	237
Ear and labyrinth disorders
Vertigo † 1	13/150 (8.67%)	23	10/152 (6.58%)	13	14/153 (9.15%)	25
Gastrointestinal disorders
Nausea † 1	37/150 (24.67%)	65	39/152 (25.66%)	66	51/153 (33.33%)	93
Constipation † 1	49/150 (32.67%)	80	39/152 (25.66%)	66	37/153 (24.18%)	57
Diarrhoea † 1	43/150 (28.67%)	124	36/152 (23.68%)	62	37/153 (24.18%)	50
Vomiting † 1	15/150 (10.00%)	24	18/152 (11.84%)	27	19/153 (12.42%)	30
Abdominal pain upper † 1	13/150 (8.67%)	18	7/152 (4.61%)	9	13/153 (8.50%)	19
Abdominal pain † 1	16/150 (10.67%)	25	9/152 (5.92%)	9	6/153 (3.92%)	7
Dyspepsia † 1	12/150 (8.00%)	17	6/152 (3.95%)	6	8/153 (5.23%)	10
Dry mouth † 1	12/150 (8.00%)	14	7/152 (4.61%)	8	4/153 (2.61%)	6
General disorders
Fatigue † 1	46/150 (30.67%)	110	51/152 (33.55%)	97	57/153 (37.25%)	101
Pyrexia † 1	32/150 (21.33%)	47	38/152 (25.00%)	63	27/153 (17.65%)	33
Oedema peripheral † 1	30/150 (20.00%)	47	35/152 (23.03%)	59	25/153 (16.34%)	35
Asthenia † 1	33/150 (22.00%)	67	22/152 (14.47%)	38	25/153 (16.34%)	39
Oedema † 1	8/150 (5.33%)	11	14/152 (9.21%)	16	7/153 (4.58%)	11
Infections and infestations
Nasopharyngitis † 1	23/150 (15.33%)	34	21/152 (13.82%)	32	26/153 (16.99%)	34
Upper respiratory tract infection † 1	16/150 (10.67%)	25	19/152 (12.50%)	23	15/153 (9.80%)	20
Bronchitis † 1	16/150 (10.67%)	25	15/152 (9.87%)	20	12/153 (7.84%)	16
Urinary tract infection † 1	12/150 (8.00%)	15	11/152 (7.24%)	15	11/153 (7.19%)	13
Investigations
Blood creatinine increased † 1	12/150 (8.00%)	21	6/152 (3.95%)	13	17/153 (11.11%)	33
Weight decreased † 1	8/150 (5.33%)	10	13/152 (8.55%)	18	9/153 (5.88%)	11
Metabolism and nutrition disorders
Anorexia † 1	24/150 (16.00%)	37	36/152 (23.68%)	54	23/153 (15.03%)	26
Hyperglycaemia † 1	12/150 (8.00%)	42	10/152 (6.58%)	32	17/153 (11.11%)	46
Hypokalaemia † 1	17/150 (11.33%)	21	12/152 (7.89%)	23	6/153 (3.92%)	6
Hypocalcaemia † 1	10/150 (6.67%)	12	8/152 (5.26%)	18	10/153 (6.54%)	25
Musculoskeletal and connective tissue disorders
Bone pain † 1	46/150 (30.67%)	96	45/152 (29.61%)	77	51/153 (33.33%)	76
Back pain † 1	16/150 (10.67%)	16	17/152 (11.18%)	23	29/153 (18.95%)	38
Musculoskeletal pain † 1	20/150 (13.33%)	37	18/152 (11.84%)	22	21/153 (13.73%)	38
Arthralgia † 1	11/150 (7.33%)	12	22/152 (14.47%)	28	17/153 (11.11%)	23
Muscle spasms † 1	19/150 (12.67%)	34	17/152 (11.18%)	36	9/153 (5.88%)	9
Pain in extremity † 1	13/150 (8.67%)	18	6/152 (3.95%)	11	10/153 (6.54%)	12
Nervous system disorders
Dizziness † 1	15/150 (10.00%)	22	20/152 (13.16%)	21	16/153 (10.46%)	21
Paraesthesia † 1	15/150 (10.00%)	19	10/152 (6.58%)	17	6/153 (3.92%)	7
Headache † 1	11/150 (7.33%)	29	16/152 (10.53%)	26	21/153 (13.73%)	21
Peripheral sensory neuropathy † 1	11/150 (7.33%)	14	9/152 (5.92%)	13	5/153 (3.27%)	10
Dysgeusia † 1	6/150 (4.00%)	9	10/152 (6.58%)	13	7/153 (4.58%)	7
Psychiatric disorders
Insomnia † 1	17/150 (11.33%)	18	20/152 (13.16%)	23	22/153 (14.38%)	35
Depression † 1	9/150 (6.00%)	12	17/152 (11.18%)	18	10/153 (6.54%)	10
Respiratory, thoracic and mediastinal disorders
Cough † 1	34/150 (22.67%)	47	27/152 (17.76%)	33	21/153 (13.73%)	29
Dyspnoea † 1	20/150 (13.33%)	34	15/152 (9.87%)	20	18/153 (11.76%)	22
Epistaxis † 1	8/150 (5.33%)	15	7/152 (4.61%)	10	11/153 (7.19%)	16
Pharyngolaryngeal pain † 1	6/150 (4.00%)	9	9/152 (5.92%)	10	9/153 (5.88%)	11
Skin and subcutaneous tissue disorders
Rash † 1	30/150 (20.00%)	62	42/152 (27.63%)	63	12/153 (7.84%)	13
Pruritus † 1	16/150 (10.67%)	24	13/152 (8.55%)	16	10/153 (6.54%)	11
Vascular disorders
Hypertension † 1	4/150 (2.67%)	5	9/152 (5.92%)	11	13/153 (8.50%)	23
Hypotension † 1	10/150 (6.67%)	13	4/152 (2.63%)	4	10/153 (6.54%)	10
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (10.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

Results Point of Contact

• Name/Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation
• Phone: 1-888-260-1599
• EMail: clinicaltrialdisclosure@celgene.com

Publications of Results:

Dimopoulos MA, Delforge M, Hajek R, Kropff M, Petrucci MT, Lewis P, Nixon A, Zhang J, Mei J, Palumbo A. Lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in newly diagnosed multiple myeloma patients aged 65 years or older: results of a randomized phase III trial. Haematologica. 2013 May;98(5):784-8. doi: 10.3324/haematol.2012.074534. Epub 2012 Dec 14.

Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W, Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M, Kloczko J, Blade J, Beksac M, Spicka I, Plesner T, Radke J, Langer C, Ben Yehuda D, Corso A, Herbein L, Yu Z, Mei J, Jacques C, Dimopoulos MA; MM-015 Investigators. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012 May 10;366(19):1759-69. doi: 10.1056/NEJMoa1112704. Erratum In: N Engl J Med. 2012 Jul 19;367(3):285.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dimopoulos MA, Petrucci MT, Foa R, Catalano J, Kropff M, Terpos E, Zhang J, Grote L, Jacques C, Palumbo A; MM-015 Investigators. Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of "progression-free survival 2" as a clinical trial end-point. Haematologica. 2015 Aug;100(8):e328-30. doi: 10.3324/haematol.2014.120790. Epub 2015 Apr 3. No abstract available.

• Responsible Party: Celgene Corporation
• ClinicalTrials.gov Identifier: NCT00405756
• Other Study ID Numbers: CC-5013-MM-015; 2006-001865-41 ( EudraCT Number )
• First Submitted: November 29, 2006
• First Posted: November 30, 2006
• Results First Submitted: April 16, 2012
• Results First Posted: May 11, 2012
• Last Update Posted: January 11, 2017