Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma (BMT CTN 0702)

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01109004
• Collaborator: Blood and Marrow Transplant Clinical Trials Network (Other), National Cancer Institute (NCI) (NIH)
• Enrollment: 758
• Locations: 54
• Arms: 3
• Actual Duration (Months): 94.1
• Patients Per Site: 14
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study is designed as a Phase III, multicenter trial of tandem autologous transplants plus maintenance therapy versus the strategy of single autologous transplant plus consolidation therapy with lenalidomide, bortezomib and dexamethasone (RVD) followed by maintenance therapy or single autologous transplant plus maintenance therapy as part of upfront treatment of multiple myeloma (MM). Lenalidomide will be used as maintenance therapy for three years in all arms.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Lenalidomide; Drug: lenalidomide, bortezomib and dexamethasone; Drug: Lenalidomide	Phase 3

Detailed Description

The primary objective of the randomized trial is to compare three-year progression-free survival (PFS) between the three treatment arms as a pairwise comparison. Mobilization therapy will not be specified for the study. Randomization to three treatment arms will be done prior to the first transplants. All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^{2 IV) given on Day -2. Upon recovery from the first transplant patients will receive either a second autologous PBSC transplant with the same conditioning regimen as the first transplant or consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40 mg on Days 1, 8 and 15, and bortezomib 1.3mg/m}2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles) or maintenance with lenalidomide (15 mg daily). All patients will also receive maintenance lenalidomide which will start after the second transplant, after the first autologous transplant or after consolidation therapy depending on the treatment arm. Maintenance therapy with lenalidomide will start at 10 mg daily for three months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 758 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Trial of Single Autologous Transplant With or Without Consolidation Therapy Versus Tandem Autologous Transplant With Lenalidomide Maintenance for Patients With Multiple Myeloma (BMT CTN 0702)
• Actual Study Start Date: May 1, 2010
• Actual Primary Completion Date: Jan 15, 2017
• Actual Study Completion Date: Mar 3, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tandem auto transplant Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance	Drug: Lenalidomide; All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.; Other Names: Revlimid™
Active Comparator: RVD consolidation Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance	Drug: lenalidomide, bortezomib and dexamethasone; All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.; Other Names: Revlimid™, Velcade®, and Decadron
Active Comparator: Lenalidomide maintenance Initial autologous transplant followed by lenalidomide maintenance	Drug: Lenalidomide; All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.; Other Names: Revlimid™

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Progression-free Survival (PFS) [38 months post-randomization]

   Progression-free survival is defined as survival without disease progression or initiation of non-protocol anti-myeloma therapy. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate progression-free survival at 38 months post-randomization.

Secondary Outcome Measures

1. Percentage of Participants With Disease Progression [38 months post-randomization]

   Disease Progression is defined as progression of multiple myeloma, including one or more of the following: A reappearance of serum monoclonal paraprotein, with a level of at least 0.5 g/dL 24-hour urine protein electrophoresis with at least 200 mg paraprotein/24 hours Abnormal free light chain levels of >10 mg/dl, only in patients without measurable paraprotein in the serum and urine At least 10% plasma cells in a bone marrow aspirate or on trephine biopsy Definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of new bone lesions or soft tissue plasmacytomas Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not attributable to any other cause To account for loss to follow-up of a few participants, the cumulative incidence of TRM at 38 months post-randomization was estimated using the Aalen-Johansen estimator, treating death prior to disease progression as a competing risk.

2. Percentage of Participants With Overall Survival (OS) [38 months post-randomization]

   Overall survival is defined as survival of death from any cause. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate overall survival at 38 months post-randomization.

3. Percentage of Participants With Treatment-related Mortality (TRM) [Up to 38 months post-randomization]

   TRM is defined as death prior to progression of multiple myeloma. To account for loss to follow-up of a few participants, the cumulative incidence of TRM at 38 months post-randomization was estimated using the Aalen-Johansen estimator, treating disease progression as a competing risk.

4. Number of Participants With Treatment Response [1 and 2 years post-randomization]

   The number of participants with very good partial response (VGPR) or better [complete response (CR), near CR (nCR), and stringent CR (sCR)] according to the International Uniform Response Criteria will be calculated. The "Worse than VGPR" group includes PR, stable disease, and progressive disease. sCR requires, in addition to CR: Normal free light chain ratio (FLC), Absence of clonal cells in bone marrow CR requires, in addition to nCR: Absence of the original monoclonal paraprotein (PPN), Disappearance of soft tissue plasmacytomas nCR is defined as: < 5% plasma cells in a bone marrow aspirate, No increase in lytic bone lesions VGPR requires: Serum or urine PPN not detectable on electrophoresis OR >=90% reduction in serum PPN plus urine PPN <100 mg/24hrs, >= 50% reduction in the level of serum monoclonal PPN or reduction in 24 hour urinary monoclonal PPN either >= 90% or to <200 mg/24 hours in light chain disease, >= 50% reduction in the size of soft tissue plasmacytomas

5. FACT-G Total Score [Up to 3 years post-randomization]

   The Functional Assessment of Cancer Therapy-General (FACT-G) is a quality of life instrument that assesses the effects of cancer therapy on a patient's physical, social/family, emotional, and functional well-being. The assessment has 27 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-108, with higher scores indicating higher levels of overall well-being.

6. FACT-BMT Score [Up to 3 years post-randomization]

   The Functional Assessment of Cancer Therapy-Bone Marrow Transplant scale (FACT-BMT) is a quality of life instrument that assesses the effects of bone marrow transplantation (BMT) on a patient's physical, social/family, emotional, and functional well-being while taking into consideration BMT-specific concerns. The assessment has 37 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-148, with higher scores indicating higher levels of overall well-being.

7. FACT-BMT Trial Outcome Index [Up to 3 years post-randomization]

   The Functional Assessment of Cancer Therapy (FACT) Trial Outcome Index is a quality of life instrument that assesses the impact of bone marrow transplantation (BMT) on a patient's physical and functional well-being while taking into consideration BMT-specific concerns. The assessment has 24 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-96, with higher scores indicating higher levels of overall well-being.

8. MOS SF-36 Physical Component Summary [Up to 3 years post-randomization]

   The Medical Outcome Study (MOS) SF-36 Physical Component Summary is a subscale of the SF-36 intended to measure physical well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.

9. MOS SF-36 Mental Component Summary [Up to 3 years post-randomization]

   The Medical Outcome Study (MOS) SF-36 Mental Component Summary is a subscale of the SF-36 intended to measure mental well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients meeting the criteria for symptomatic multiple myeloma (MM).

• Patients who are 70 years of age, or younger, at time of enrollment.

• Patients who have received at least two cycles of any regimen as initial systemic therapy and are within 2 - 12 months of the first dose of initial therapy.

• Cardiac function: left ventricular ejection fraction at rest greater than 40 percent.

• Hepatic: bilirubin less than 1.5x the upper limit of normal and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 2.5x the upper limit of normal. (Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the defined bilirubin value of 1.5x the upper limit of normal.)

• Renal: Creatinine clearance of grater than or equal to 40 mL/min, estimated or calculated.

• Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) greater than 50 percent of predicted value (corrected for hemoglobin).

• Patients with an adequate autologous graft defined as a cryopreserved PBSC graft containing greater than or equal to 4 x 10^{6 CD34+ cells/kg patient weight. The graft may not be CD34+ selected or otherwise manipulated to remove tumor or other cells. The graft can be collected at the transplanting institution or by a referring center. The autograft must be stored so that there are two products each containing at least 2 x 10}6 CD34+ cells/kg patient weight.

• Signed informed consent form.

Exclusion Criteria:

• Patients who never fulfill the criteria for symptomatic MM.

• Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques]. Patients with light chain MM detected in the serum by free light chain assay are eligible.

• Patients with plasma cell leukemia.

• Karnofsky performance score less than 70 percent.

• Patients with greater than grade 2 sensory neuropathy (CTCAE).

• Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms).

• Patients seropositive for the human immunodeficiency virus (HIV).

• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.

• Patient has hypersensitivity to bortezomib, boron or mannitol.

• Patient has received other investigational drugs with 14 days before enrollment.

• Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs. Cancer treated with curative intent greater than 5 years previously is allowed.

• Female patients who are pregnant (positive B-HCG) or breastfeeding.

• Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use contraceptive techniques during the length of lenalidomide maintenance therapy.

• Prior allograft or prior autograft.

• Patients who have received mid-intensity melphalan (greater than 50 mg IV) as part of prior therapy.

• Patients unable or unwilling to provide informed consent.

• Prior organ transplant requiring immunosuppressive therapy.

• Patients with disease progression prior to enrollment.

• Patients who have received lenalidomide as initial therapy for MM and have experienced toxicities resulting in treatment discontinuation.

• Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide or thalidomide.

• Patients unwilling to take deep vein thrombosis (DVT) prophylaxis.

• Patients who cannot undergo an intervention in any treatment arm due to a priori denial of medical costs coverage by third party payers.

• Patients unable to unwilling to return to the transplant center for their assigned treatments.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cancer Center	Tucson	Arizona	United States	85724
2	City of Hope National Medical Center	Duarte	California	United States	91010-3000
3	UCSD Medical Center	La Jolla	California	United States	92093
4	University of California, San Francisco	San Francisco	California	United States	94143-0324
5	Stanford Hospital and Clinics	Stanford	California	United States	94305
6	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
7	Christiana Care Health System	Newark	Delaware	United States	19718
8	University of Florida College of Medicine	Gainesville	Florida	United States	32610
9	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
10	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33624
11	Blood and Marrow Transplant Program at Northside Hospital	Atlanta	Georgia	United States	30342
12	Georgia Health Sciences University	Augusta	Georgia	United States	30912
13	St. Lukes Mountain States Tumor Institute	Boise	Idaho	United States	83712
14	Rush University Medical Center	Chicago	Illinois	United States	60612
15	University of Illinois	Chicago	Illinois	United States	60612
16	Advocate Lutheran General Hospital	Park Ridge	Illinois	United States	60068
17	University of Kansas Hospital	Kansas City	Kansas	United States	66160
18	Wichita CCOP	Wichita	Kansas	United States	67214
19	University of Kentucky	Lexington	Kentucky	United States	40536
20	Louisiana State University Health Sciences Center	Shreveport	Louisiana	United States	71130
21	DFCI, Brigham and Womens Hospital	Boston	Massachusetts	United States	02114
22	DFCI, Massachusetts General Hospital	Boston	Massachusetts	United States	02114
23	University of Michigan Medical Center	Ann Arbor	Michigan	United States	48105-2967
24	Karmanos Cancer Institute/BMT	Detroit	Michigan	United States	48201
25	University of Minnesota	Minneapolis	Minnesota	United States	55455
26	Washington University, Barnes Jewish Hospital	Saint Louis	Missouri	United States	63110
27	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
28	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
29	Roswell Park Cancer Center	Buffalo	New York	United States	14263
30	North Shore University Hospital	Lake Success	New York	United States	11042
31	Mount Sinai Medical Center	New York	New York	United States	10029
32	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10174
33	University of Rochester Medical Center	Rochester	New York	United States	14642
34	University of North Carolina Hospital at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7305
35	Duke University Medical Center	Durham	North Carolina	United States	27705
36	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
37	Jewish Hospital BMT Program	Cincinnati	Ohio	United States	45236
38	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106-5061
39	Ohio State/Arthur G. James Cancer Hospital	Columbus	Ohio	United States	43210
40	University of Oklahoma Medical Center	Oklahoma City	Oklahoma	United States	73104
41	Oregon Health & Science University	Portland	Oregon	United States	97239-3098
42	Penn State College of Medicine, The Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
43	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104
44	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
45	Sarah Cannon Blood & Marrow Transplant Program	Nashville	Tennessee	United States	37203
46	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232-8210
47	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
48	Baylor College of Medicine/The Methodist Hospital	Houston	Texas	United States	77030
49	University of Texas, MD Anderson CRC	Houston	Texas	United States	77030
50	Texas Transplant Institute	San Antonio	Texas	United States	78229
51	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024
52	West Virginia University Hospital	Morgantown	West Virginia	United States	26506
53	University of Wisconsin Hospital & Clinics	Madison	Wisconsin	United States	53792-5156
54	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53211

Sponsors and Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• Blood and Marrow Transplant Clinical Trials Network
• National Cancer Institute (NCI)

Investigators

• Study Director: Mary Horowitz, MD, Center for International Blood and Marrow Transplant Research

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Blood and Marrow Transplant Clinical Trials Network Website
• National Marrow Donor Program

Publications

None provided.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT01109004
• Other Study ID Numbers: BMTCTN0702; BMT CTN 0702; U01HL069294-05; 690; NCT02257515
• First Posted: Apr 22, 2010
• Last Update Posted: Dec 9, 2021
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by National Heart, Lung, and Blood Institute (NHLBI): Symptomatic Multiple Myeloma; Lenalidomide; Anti-Myeloma Agents; Hematologic Disorders; Maintenance Therapy; Progression; Autologous Transplant; RVD Consolidation
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Lenalidomide; Bortezomib

Study Results

Participant Flow

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Period Title: Overall Study
STARTED	247	254	257
COMPLETED	247	254	257
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance	Total
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Total of all reporting groups
Overall Participants	247	254	257	758
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56	57	56	56
Sex: Female, Male (Count of Participants)
Female	100 40.5%	108 42.5%	96 37.4%	304 40.1%
Male	147 59.5%	146 57.5%	161 62.6%	454 59.9%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	178 72.1%	192 75.6%	201 78.2%	571 75.3%
African American	50 20.2%	39 15.4%	41 16%	130 17.2%
Multiple/Other/Unknown	19 7.7%	23 9.1%	15 5.8%	57 7.5%
Karnofsky Performance Score (KPS) (Count of Participants)
90 or Greater	182 73.7%	169 66.5%	172 66.9%	523 69%
Less Than 90	65 26.3%	85 33.5%	85 33.1%	235 31%
Disease Risk (Count of Participants)
Standard	175 70.9%	178 70.1%	182 70.8%	535 70.6%
High	72 29.1%	76 29.9%	75 29.2%	223 29.4%
Initial Therapy (Count of Participants)
Bortezomib/Lenalidomide/Dexamethasone	141 57.1%	136 53.5%	143 55.6%	420 55.4%
Bortezomib/Cyclophosphamide/Dexamethasone	33 13.4%	35 13.8%	40 15.6%	108 14.2%
Lenalidomide/Dexamethasone	24 9.7%	28 11%	22 8.6%	74 9.8%
Bortezomib/Dexamethasone	29 11.7%	32 12.6%	32 12.5%	93 12.3%
Other	19 7.7%	19 7.5%	20 7.8%	58 7.7%
Unknown	1 0.4%	4 1.6%	0 0%	5 0.7%
Time from Initial Therapy to Enrollment (months) [Median (Full Range) ]
Median (Full Range) [months]	5	5	5	5
Number of Lines of Therapy (Count of Participants)
1	210 85%	213 83.9%	218 84.8%	641 84.6%
2	31 12.6%	36 14.2%	37 14.4%	104 13.7%
3	5 2%	1 0.4%	2 0.8%	8 1.1%
Unknown	1 0.4%	4 1.6%	0 0%	5 0.7%
Disease Status at Enrollment (Count of Participants)
Stringent Complete Response	21 8.5%	26 10.2%	23 8.9%	70 9.2%
Complete Response	22 8.9%	19 7.5%	24 9.3%	65 8.6%
Near Complete Response	27 10.9%	22 8.7%	24 9.3%	73 9.6%
Very Good Partial Response	52 21.1%	53 20.9%	43 16.7%	148 19.5%
Partial Response	106 42.9%	108 42.5%	123 47.9%	337 44.5%
Stable Disease	14 5.7%	21 8.3%	14 5.4%	49 6.5%
Progression	4 1.6%	2 0.8%	3 1.2%	9 1.2%
Not Evaluable	1 0.4%	3 1.2%	3 1.2%	7 0.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Progression-free Survival (PFS)
Description	Progression-free survival is defined as survival without disease progression or initiation of non-protocol anti-myeloma therapy. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate progression-free survival at 38 months post-randomization.
Time Frame	38 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Measure Participants	247	254	257
Number (95% Confidence Interval) [percentage of participants]	58.5 23.7%	57.8 22.8%	53.9 21%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, RVD Consolidation
	Comments	The null hypothesis is that the percentages of participants with PFS at 38 months post-randomization are equal for those receiving Tandem auto transplant and RVD consolidation therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments	The primary analysis involved pairwise comparisons of PFS between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Log Rank
	Comments	The log rank test was stratified on risk status (high risk vs. standard risk)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with PFS at 38 months post-randomization are equal for those receiving Tandem auto transplant and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments	The primary analysis involved pairwise comparisons of PFS between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Log Rank
	Comments	The log rank test was stratified on risk status (high risk vs. standard risk)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	RVD Consolidation, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with PFS at 38 months post-randomization are equal for those receiving RVD consolidation and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments	The primary analysis involved pairwise comparisons of PFS between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Log Rank
	Comments	The log rank test was stratified on risk status (high risk vs. standard risk)

2. Secondary Outcome

Title	Percentage of Participants With Disease Progression
Description	Disease Progression is defined as progression of multiple myeloma, including one or more of the following: A reappearance of serum monoclonal paraprotein, with a level of at least 0.5 g/dL 24-hour urine protein electrophoresis with at least 200 mg paraprotein/24 hours Abnormal free light chain levels of >10 mg/dl, only in patients without measurable paraprotein in the serum and urine At least 10% plasma cells in a bone marrow aspirate or on trephine biopsy Definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of new bone lesions or soft tissue plasmacytomas Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not attributable to any other cause To account for loss to follow-up of a few participants, the cumulative incidence of TRM at 38 months post-randomization was estimated using the Aalen-Johansen estimator, treating death prior to disease progression as a competing risk.
Time Frame	38 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Measure Participants	247	254	257
Number (95% Confidence Interval) [percentage of participants]	39.8 16.1%	41.0 16.1%	45.6 17.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, RVD Consolidation
	Comments	The null hypothesis is that the percentages of participants with disease progression at 38 months post-randomization are equal for those receiving Tandem auto transplant and RVD consolidation therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments	Two sided testing was performed at a significance level of 0.05
	Method	Gray's test
	Comments	Death prior to disease progression was treated as a competing risk

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with disease progression at 38 months post-randomization are equal for those receiving Tandem auto transplant and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.21
	Comments	Two sided testing was performed at a significance level of 0.05
	Method	Gray's test
	Comments	Death prior to disease progression was treated as a competing risk

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	RVD Consolidation, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with disease progression at 38 months post-randomization are equal for those receiving RVD consolidation and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments	Two sided testing was performed at a significance level of 0.05
	Method	Gray's test
	Comments	Death prior to disease progression was treated as a competing risk

3. Secondary Outcome

Title	Percentage of Participants With Overall Survival (OS)
Description	Overall survival is defined as survival of death from any cause. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate overall survival at 38 months post-randomization.
Time Frame	38 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Measure Participants	247	254	257
Number (95% Confidence Interval) [percentage of participants]	81.8 33.1%	85.4 33.6%	83.7 32.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, RVD Consolidation
	Comments	The null hypothesis is that the percentages of participants with OS at 38 months post-randomization are equal for those receiving Tandem auto transplant and RVD consolidation therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	Two sided testing was performed at a significance level of 0.05
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with OS at 38 months post-randomization are equal for those receiving Tandem auto transplant and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments	Two sided testing was performed at a significance level of 0.05
	Method	Log Rank
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	RVD Consolidation, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with OS at 38 months post-randomization are equal for those receiving RVD consolidation and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments	Two sided testing was performed at a significance level of 0.05
	Method	Log Rank
	Comments

4. Secondary Outcome

Title	Percentage of Participants With Treatment-related Mortality (TRM)
Description	TRM is defined as death prior to progression of multiple myeloma. To account for loss to follow-up of a few participants, the cumulative incidence of TRM at 38 months post-randomization was estimated using the Aalen-Johansen estimator, treating disease progression as a competing risk.
Time Frame	Up to 38 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Measure Participants	247	254	257
Number (95% Confidence Interval) [percentage of participants]	1.7 0.7%	1.2 0.5%	0.5 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, RVD Consolidation
	Comments	The null hypothesis is that the percentages of participants with TRM at 38 months post-randomization are equal for those receiving Tandem auto transplant and RVD consolidation therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments	Two sided testing was performed at a significance level of 0.05
	Method	Gray's test
	Comments	Death prior to disease progression was treated as a competing risk

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with TRM at 38 months post-randomization are equal for those receiving Tandem auto transplant and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments	Two sided testing was performed at a significance level of 0.05
	Method	Gray's test
	Comments	Death prior to disease progression was treated as a competing risk

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	RVD Consolidation, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with TRM at 38 months post-randomization are equal for those receiving RVD consolidation and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments	Two sided testing was performed at a significance level of 0.05
	Method	Gray's test
	Comments	Death prior to disease progression was treated as a competing risk

5. Secondary Outcome

Title	Number of Participants With Treatment Response
Description	The number of participants with very good partial response (VGPR) or better [complete response (CR), near CR (nCR), and stringent CR (sCR)] according to the International Uniform Response Criteria will be calculated. The "Worse than VGPR" group includes PR, stable disease, and progressive disease. sCR requires, in addition to CR: Normal free light chain ratio (FLC), Absence of clonal cells in bone marrow CR requires, in addition to nCR: Absence of the original monoclonal paraprotein (PPN), Disappearance of soft tissue plasmacytomas nCR is defined as: < 5% plasma cells in a bone marrow aspirate, No increase in lytic bone lesions VGPR requires: Serum or urine PPN not detectable on electrophoresis OR >=90% reduction in serum PPN plus urine PPN <100 mg/24hrs, >= 50% reduction in the level of serum monoclonal PPN or reduction in 24 hour urinary monoclonal PPN either >= 90% or to <200 mg/24 hours in light chain disease, >= 50% reduction in the size of soft tissue plasmacytomas
Time Frame	1 and 2 years post-randomization

Outcome Measure Data

Analysis Population Description

Only participants that were evaluable for disease response were analyzed at each time point. Those who had died or experienced disease progression were excluded.

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Measure Participants	247	254	257
CR or sCR	97 39.3%	122 48%	98 38.1%
VGPR or nCR	56 22.7%	50 19.7%	60 23.3%
Worse than VGPR	39 15.8%	37 14.6%	50 19.5%
CR or sCR	98 39.7%	117 46.1%	93 36.2%
VGPR or nCR	39 15.8%	37 14.6%	41 16%
Worse than VGPR	20 8.1%	21 8.3%	26 10.1%

6. Secondary Outcome

Title	FACT-G Total Score
Description	The Functional Assessment of Cancer Therapy-General (FACT-G) is a quality of life instrument that assesses the effects of cancer therapy on a patient's physical, social/family, emotional, and functional well-being. The assessment has 27 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-108, with higher scores indicating higher levels of overall well-being.
Time Frame	Up to 3 years post-randomization

Outcome Measure Data

Analysis Population Description

Outcomes are analyzed from participants that were alive, progression-free, and completed assessments.

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Measure Participants	247	254	257
Baseline	79 (1.0)	79 (1.0)	77 (1.0)
1 Year	84 (1.3)	84 (1.3)	83 (1.2)
2 Years	84 (1.5)	84 (1.3)	85 (1.4)
3 Years	85 (1.6)	84 (1.6)	85 (1.7)

7. Secondary Outcome

Title	FACT-BMT Score
Description	The Functional Assessment of Cancer Therapy-Bone Marrow Transplant scale (FACT-BMT) is a quality of life instrument that assesses the effects of bone marrow transplantation (BMT) on a patient's physical, social/family, emotional, and functional well-being while taking into consideration BMT-specific concerns. The assessment has 37 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-148, with higher scores indicating higher levels of overall well-being.
Time Frame	Up to 3 years post-randomization

Outcome Measure Data

Analysis Population Description

Outcomes are analyzed from participants that were alive, progression-free, and completed assessments.

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Measure Participants	247	254	257
Baseline	107 (1.4)	107 (1.3)	105 (1.3)
1 Year	113 (1.7)	115 (1.7)	113 (1.6)
2 Years	114 (1.8)	115 (1.7)	115 (1.7)
3 Years	115 (2.0)	114 (2.1)	115 (2.2)

8. Secondary Outcome

Title	FACT-BMT Trial Outcome Index
Description	The Functional Assessment of Cancer Therapy (FACT) Trial Outcome Index is a quality of life instrument that assesses the impact of bone marrow transplantation (BMT) on a patient's physical and functional well-being while taking into consideration BMT-specific concerns. The assessment has 24 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-96, with higher scores indicating higher levels of overall well-being.
Time Frame	Up to 3 years post-randomization

Outcome Measure Data

Analysis Population Description

Outcomes are analyzed from participants that were alive, progression-free, and completed assessments.

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Measure Participants	247	254	257
Baseline	64 (1.1)	65 (1.0)	63 (1.0)
1 Year	70 (1.2)	72 (1.2)	71 (1.1)
2 Years	73 (1.2)	73 (1.3)	73 (1.2)
3 Years	73 (1.4)	71 (1.5)	73 (1.5)

9. Secondary Outcome

Title	MOS SF-36 Physical Component Summary
Description	The Medical Outcome Study (MOS) SF-36 Physical Component Summary is a subscale of the SF-36 intended to measure physical well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.
Time Frame	Up to 3 years post-randomization

Outcome Measure Data

Analysis Population Description

Outcomes are analyzed from participants that were alive, progression-free, and completed assessments.

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Measure Participants	247	254	257
Baseline	37 (0.7)	39 (0.7)	38 (0.7)
1 Year	43 (0.8)	43 (0.8)	42 (0.7)
2 Years	44 (0.8)	44 (0.9)	43 (0.9)
3 Years	42 (1.0)	42 (1.0)	43 (1.0)

10. Secondary Outcome

Title	MOS SF-36 Mental Component Summary
Description	The Medical Outcome Study (MOS) SF-36 Mental Component Summary is a subscale of the SF-36 intended to measure mental well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.
Time Frame	Up to 3 years post-randomization

Outcome Measure Data

Analysis Population Description

Outcomes are analyzed from participants that were alive, progression-free, and completed assessments.

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Measure Participants	247	254	257
Baseline	49 (0.7)	48 (0.7)	48 (0.8)
1 Year	50 (0.9)	51 (0.8)	50 (0.8)
2 Years	50 (1.0)	50 (0.8)	50 (1.0)
3 Years	51 (1.0)	50 (1.1)	51 (1.0)

Adverse Events

Arm/Group Title	Tandem Auto Transplant		RVD Consolidation		Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.		Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.		Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
All Cause Mortality
	Tandem Auto Transplant		RVD Consolidation		Lenalidomide Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tandem Auto Transplant		RVD Consolidation		Lenalidomide Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/247 (17%)		45/254 (17.7%)		53/257 (20.6%)
Blood and lymphatic system disorders
Haemolytic anaemia	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Splenic infarction	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Cardiac disorders
Acute myocardial infarction	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Atrial fibrillation	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Bradycardia	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Cardiac failure congestive	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Cardiac tamponade	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Cardiac valve disease	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Cardio-respiratory arrest	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Left ventricular failure	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Myocardial infarction	2/247 (0.8%)	2	1/254 (0.4%)	1	1/257 (0.4%)	1
Sinus bradycardia	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Supraventricular tachycardia	1/247 (0.4%)	1	1/254 (0.4%)	1	0/257 (0%)	0
Torsade de pointes	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Eye disorders
Cataract	1/247 (0.4%)	1	0/254 (0%)	0	1/257 (0.4%)	1
Gastrointestinal disorders
Abdominal pain	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Abdominal pain upper	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Colitis ischaemic	0/247 (0%)	0	2/254 (0.8%)	2	0/257 (0%)	0
Gastric haemorrhage	0/247 (0%)	0	0/254 (0%)	0	2/257 (0.8%)	2
Gastrointestinal haemorrhage	0/247 (0%)	0	0/254 (0%)	0	2/257 (0.8%)	2
Haemorrhoids	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Impaired gastric emptying	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Inguinal hernia, obstructive	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Pancreatitis	0/247 (0%)	0	1/254 (0.4%)	1	1/257 (0.4%)	1
Small intestinal obstruction	2/247 (0.8%)	2	1/254 (0.4%)	1	4/257 (1.6%)	4
Hepatobiliary disorders
Bile duct stone	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Cholecystitis	1/247 (0.4%)	1	0/254 (0%)	0	3/257 (1.2%)	3
Cholecystitis acute	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Infections and infestations
Appendicitis	0/247 (0%)	0	0/254 (0%)	0	2/257 (0.8%)	2
Gastroenteritis viral	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Injury, poisoning and procedural complications
Cervical vertebral fracture	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Fall	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Fracture	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Hip fracture	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Subdural haematoma	0/247 (0%)	0	1/254 (0.4%)	1	2/257 (0.8%)	2
Investigations
Arthroscopy	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Aspartate aminotransferase increased	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Hepatic enzyme increased	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Musculoskeletal and connective tissue disorders
Bone pain	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Joint range of motion decreased	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Muscular weakness	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Rhabdomyolysis	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Acute myeloid leukaemia	0/247 (0%)	0	3/254 (1.2%)	3	0/257 (0%)	0
Acute promyelocytic leukaemia	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Adenocarcinoma	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Basal cell carcinoma	1/247 (0.4%)	1	0/254 (0%)	0	1/257 (0.4%)	1
Bladder cancer	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Breast cancer	0/247 (0%)	0	1/254 (0.4%)	1	1/257 (0.4%)	1
Colon cancer	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Colon cancer metastatic	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Endometrial cancer	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Gastric cancer	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Glioblastoma	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Hodgkin's disease	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Intraductal proliferative breast lesion	0/247 (0%)	0	0/254 (0%)	0	2/257 (0.8%)	2
Malignant melanoma	1/247 (0.4%)	1	0/254 (0%)	0	1/257 (0.4%)	1
Metastasis	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Myelodysplastic syndrome	2/247 (0.8%)	2	3/254 (1.2%)	3	0/257 (0%)	0
Papillary thyroid cancer	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Prostate cancer	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Transitional cell carcinoma	0/247 (0%)	0	1/254 (0.4%)	1	1/257 (0.4%)	1
Nervous system disorders
Autonomic neuropathy	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Cerebral ischaemia	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Cerebral venous thrombosis	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Cerebrovascular accident	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Dizziness	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Haemorrhage intracranial	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Neuropathy peripheral	1/247 (0.4%)	1	1/254 (0.4%)	1	0/257 (0%)	0
Posterior reversible encephalopathy syndrome	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Spinal cord compression	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Syncope	1/247 (0.4%)	1	3/254 (1.2%)	3	0/257 (0%)	0
Psychiatric disorders
Mania	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Mental status changes	0/247 (0%)	0	1/254 (0.4%)	1	1/257 (0.4%)	1
Renal and urinary disorders
Acute kidney injury	2/247 (0.8%)	2	0/254 (0%)	0	2/257 (0.8%)	2
Renal failure	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Acute respiratory failure	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Hypoxia	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Interstitial lung disease	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Pleural effusion	4/247 (1.6%)	4	1/254 (0.4%)	1	1/257 (0.4%)	1
Pulmonary embolism	1/247 (0.4%)	1	0/254 (0%)	0	4/257 (1.6%)	4
Pulmonary hypertension	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Respiratory distress	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Respiratory failure	0/247 (0%)	0	1/254 (0.4%)	1	1/257 (0.4%)	1
Surgical and medical procedures
Cataract operation	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Cholecystectomy	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Umbilical hernia repair	0/247 (0%)	0	0/254 (0%)	0	1/257 (0.4%)	1
Vascular disorders
Deep vein thrombosis	2/247 (0.8%)	2	1/254 (0.4%)	1	1/257 (0.4%)	1
Hypotension	1/247 (0.4%)	1	0/254 (0%)	0	0/257 (0%)	0
Superior vena cava syndrome	0/247 (0%)	0	1/254 (0.4%)	1	0/257 (0%)	0
Other (Not Including Serious) Adverse Events
	Tandem Auto Transplant		RVD Consolidation		Lenalidomide Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/247 (0%)		0/254 (0%)		0/257 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.