Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02874742
Collaborator
(none)
224
36
2
67.3
6.2
0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if the addition of daratumumab to lenalidomide-bortezomib-dexamethasone (RVd) will increase the proportion of participants achieving stringent complete response (sCR), as defined by the International Myeloma Working Group (IMWG) criteria, by the time of completion of post autologous stem cell transplantation (ASCT) consolidation treatment, compared with RVd alone.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
224 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 2, Randomized, Open-Label Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma Eligible for High-Dose Chemotherapy and Autologous Stem Cell Transplantation
Actual Study Start Date :
Aug 29, 2016
Actual Primary Completion Date :
Jan 25, 2019
Actual Study Completion Date :
Apr 8, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd)

Participants will receive lenalidomide, bortezomib, dexamethasone and daratumumab.

Drug: Lenalidomide
Cycles 1 through 6: lenalidomide 25 (milligram) mg orally on Days 1 through 14 and each cycle is of 21-days followed by maintenance treatment with lenalidomide 10 mg on days 1-21 throughout each 28-day cycle on Cycles 7 through 9. Beginning at Cycle 10, the lenalidomide dose will be increased to 15 mg unless there is a tolerability concern.

Drug: Bortezomib
Bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 4, 8, and 11 during Cycles 1-6.

Drug: Dexamethasone
Dexamethasone 40 mg orally every week (20 mg on Days 1, 2, 8, 9, 15, and 16).

Drug: Daratumumab
Daratumumab intravenously at a dose of 16 milligram per kilogram (mg/kg) weekly during induction treatment (Days 1, 8, and 15 of Cycles 1 through 4), and every 3 weeks during consolidation treatment (Day 1 of Cycles 5 and 6), followed by maintenance treatment with daratumumab every 4 or 8 weeks.

Experimental: Lenalidomide+Bortezomib+Dexamethasone (RVd)

Participants will receive lenalidomide, bortezomib and dexamethasone.

Drug: Lenalidomide
Cycles 1 through 6: lenalidomide 25 (milligram) mg orally on Days 1 through 14 and each cycle is of 21-days followed by maintenance treatment with lenalidomide 10 mg on days 1-21 throughout each 28-day cycle on Cycles 7 through 9. Beginning at Cycle 10, the lenalidomide dose will be increased to 15 mg unless there is a tolerability concern.

Drug: Bortezomib
Bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 4, 8, and 11 during Cycles 1-6.

Drug: Dexamethasone
Dexamethasone 40 mg orally every week (20 mg on Days 1, 2, 8, 9, 15, and 16).

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants With Stringent Complete Response (sCR) [From randomization to post-ASCT consolidation (after Cycle 6) before maintenance treatment (up to 10 months)]

    Percentage of participants who have achieved sCR as determined by the validated computer algorithm according to the International Myeloma Working Group (IMWG) criteria, by the end of post-autologous stem cell transplantation (post-ASCT) consolidation treatment were reported. Complete response (CR) is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (<) 5 percent (%) PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.

Secondary Outcome Measures

  1. Percentage of Participants With Overall Complete Response (CR) [From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months)]

    Overall CR rate is defined as the percentage of participants who achieve CR, according to the IMWG criteria. CR is negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5% PCs in bone marrow.

  2. Percentage of Participants With Overall Stringent Complete Response (sCR) [From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months)]

    Overall sCR rate is defined as the percentage of participants who achieved sCR, according to the IMWG criteria. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5 % PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.

  3. Percentage of Participants With Overall Response Rate (ORR) [From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months)]

    ORR -percentage of participants who achieved partial response (PR) or better (PR, Very Good Partial Response [VGPR], CR or sCR) based on computerized algorithm as per IMWG criteria. PR -greater than or equal to (>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg//24 hours. If serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required. A >=50% reduction in the size of soft tissue plasmacytomas is also required; VGPR-serum and urine M-component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours; CR-negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. sCR- in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.

  4. Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better [From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months)]

    VGPR or better rate is defined as the percentage of participants who achieved VGPR or better, according to the IMWG criteria. VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours.

  5. Percentage of Participants With Negative Minimal Residual Disease (MRD) [From randomization to end of following: induction treatment, post-ASCT consolidation (after Cycle 6) (up to 4.5 months)]

    Minimal residual disease negative rate is defined as the percentage of participants who achieve MRD negative status by the respective time point. Minimal residual disease was evaluated in participants who achieved CR or sCR (including participants with VGPR or better and suspected daratumumab interference) using next-generation sequencing which utilizes multiple myeloma cell DNA from bone marrow aspirates at a threshold of less than (<) 10^5.

  6. Duration of Complete Response [From randomization to the date of first documented evidence of progressive disease or relapse from CR (up to 2 years and 5 months)]

    Duration of CR is the duration from the date of initial documentation of a CR response, according to the IMWG criteria, to the date of first documented evidence of progressive disease (PR), or relapse from CR. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to [>=] 0.5 gram per deciliter [g/dL] and >=200 milligram [mg]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to Plasma cell (PC) proliferative disorder.

  7. Duration of Stringent Complete Response (sCR) [From randomization to the date of first documented evidence of progressive disease or relapse from sCR (up to 2 years and 5 months)]

    Duration of sCR is the duration from the date of initial documentation of a sCR response, according to the IMWG criteria, to the date of first documented evidence of progressive disease, or relapse from sCR. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

  8. Time to Stringent Complete Response (sCR) [From randomization to the date of initial documentation of sCR (up to 2 years and 5 months)]

    Time to sCR is the duration from the date of randomization to the date of initial documentation of sCR, which was confirmed by a repeated measurement as required by the IMWG criteria.

  9. Time to Complete Response or Better [From randomization to the date of initial documentation of CR (Up to 2 years and 5 months)]

    Time to CR or better is the duration from the date of randomization to the date of initial documentation of CR or better, which was confirmed by a repeated measurement as required by the IMWG criteria.

  10. Time to Very Good Partial Response (VGPR) or Better [From randomization to the date of initial documentation of VGPR or better (up to 2 years and 5 months)]

    Time to VGPR or better is the duration from the date of randomization to the date of initial documentation of VGPR or better, which was confirmed by a repeated measurement as required by the IMWG criteria.

  11. Time to Partial Response (PR) or Better [From randomization to the date of initial documentation of PR or better (up to 2 years and 5 months)]

    Time to PR or better is the duration from the date of randomization to the date of initial documentation of PR or better, which was confirmed by a repeated measurement as required by the IMWG criteria.

  12. Progression-free Survival (PFS) [Up to 24 months]

    PFS is defined as the duration from the date of randomization to the date of first documented evidence of progressive disease or death, whichever comes first. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

  13. Overall Survival (OS) [From randomization to the date of initial documentation of participant's death (up to 2 years and 5 months)]

    OS is measured from the date of randomization to the date of the participant's death.

  14. Time to Progression (TTP) [From randomization to the date of first documented evidence of progressive disease (up to 2 years and 5 months)]

    TTP is defined as the duration from the date of randomization to the date of first documented evidence of progressive disease according to the IMWG criteria.

  15. Duration of Response [From the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive (up to 2 years and 5 months)]

    Duration of response is defined as the duration from the date of initial documentation of a response (PR or better) according to the IMWG criteria to the date of first documented evidence of progressive disease according to the IMWG criteria. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Considered by the investigator to be eligible for high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) according to the institution's criteria based on age, medical history, cardiac and pulmonary status, overall health and condition, co-morbid condition(s), physical examination, and laboratory studies

  • Has not had prior systemic therapy for multiple myeloma. An emergency course of steroids (defined as no greater than 40 milligram [mg] of dexamethasone, or equivalent per day for a maximum of 4 days (that is, a total of 160 mg) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles 1-2 of study treatment as needed for lytic bone disease

  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

  • Woman of childbearing potential must have 2 negative highly sensitive serum (beta-human chorionic gonadotropin [b-hCG]) during screening, the first one within 10 to 14 days prior to the first dose of any component of study treatment and the second within 24 hours prior to the first dose of any component of study treatment

  • A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study (including during dose interruptions), and for 4 weeks following discontinuation of lenalidomide, and if receiving daratumumab, for 3 months after the last dose

Exclusion Criteria:
  • Diagnosed or treated for malignancy other than multiple myeloma, except: a) Malignancy treated with curative intent and with no known active disease present for more than equal to (>= )3 years before randomization; b) Adequately treated non-melanoma skin cancer, lentigo maligna or in situ malignancies (including but not limited to, cervical, breast) with no evidence of disease

  • Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma

  • Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) less than (<)50 percent (%) of predicted normal

  • Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification

  • Known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C. Participants who completed treatment for hepatitis C at least 6 months prior to screening and have no detectable circulating hepatitis C virus (HCV) at screening, may participate in the study. Such participants will be required to undergo regular assessment for HCV reactivation during their participation in the study. Participants who test positive for HCV at any time during these assessments will be withdrawn from the study

Contacts and Locations

Locations

Site City State Country Postal Code
1 Birmingham Alabama United States
2 Duarte California United States
3 La Jolla California United States
4 Los Angeles California United States
5 San Francisco California United States
6 Aurora Colorado United States
7 Washington District of Columbia United States
8 Orlando Florida United States
9 Tampa Florida United States
10 Atlanta Georgia United States
11 Chicago Illinois United States
12 Westwood Kansas United States
13 New Orleans Louisiana United States
14 Baltimore Maryland United States
15 Boston Massachusetts United States
16 Worcester Massachusetts United States
17 Detroit Michigan United States
18 Saint Louis Missouri United States
19 Omaha Nebraska United States
20 Buffalo New York United States
21 New York New York United States
22 Chapel Hill North Carolina United States
23 Charlotte North Carolina United States
24 Durham North Carolina United States
25 Winston-Salem North Carolina United States
26 Columbus Ohio United States
27 Portland Oregon United States
28 Abington Pennsylvania United States
29 Philadelphia Pennsylvania United States
30 Nashville Tennessee United States
31 Dallas Texas United States
32 Houston Texas United States
33 Salt Lake City Utah United States
34 Seattle Washington United States
35 Spokane Washington United States
36 Milwaukee Wisconsin United States

Sponsors and Collaborators

  • Janssen Research & Development, LLC

Investigators

  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02874742
Other Study ID Numbers:
  • CR108195
  • 54767414MMY2004
First Posted:
Aug 22, 2016
Last Update Posted:
Jun 7, 2022
Last Verified:
May 1, 2022
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details 223 participants were enrolled/randomized (16 in safety run-in,104 to D-RVd and 103 to RVd group). At clinical cut-off, among 207 (D-RVd [104]+RVd [103]) randomized, 201 received treatment (D-RVd: 100 and RVd: 101). 1 participant randomized to D-RVd group received RVd treatment and was randomized twice (resulting a total of 224 participants).
Pre-assignment Detail Participant was screen-failure and was randomized to D-RVd first; after re-screening was randomized to RVd group.The participant was counted in D-RVd for ITT analysis and RVd for safety analysis. So, safety analysis set included 99 participants in D-RVd and 102 in RVd group who received at least 1 dose of study treatment.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVD
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Period Title: Overall Study
STARTED 103 104 16
Safety 102 99 16
COMPLETED 0 0 0
NOT COMPLETED 103 104 16

Baseline Characteristics

Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVD Total
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Total of all reporting groups
Overall Participants 102 99 16 217
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
59
(7.25)
57.1
(9.96)
59.8
(5.96)
58.2
(8.55)
Sex: Female, Male (Count of Participants)
Female
44
43.1%
43
43.4%
8
50%
95
43.8%
Male
58
56.9%
56
56.6%
8
50%
122
56.2%
Race/Ethnicity, Customized (Count of Participants)
Asian
2
2%
0
0%
1
6.3%
3
1.4%
Black or African American
18
17.6%
14
14.1%
4
25%
36
16.6%
More than one race
1
1%
0
0%
0
0%
1
0.5%
Other
1
1%
1
1%
0
0%
2
0.9%
Unknown or Not Reported
6
5.9%
1
1%
0
0%
7
3.2%
White
74
72.5%
83
83.8%
11
68.8%
168
77.4%
Region of Enrollment (Count of Participants)
UNITED STATES
102
100%
99
100%
16
100%
217
100%

Outcome Measures

1. Primary Outcome
Title Percentage of Participants With Stringent Complete Response (sCR)
Description Percentage of participants who have achieved sCR as determined by the validated computer algorithm according to the International Myeloma Working Group (IMWG) criteria, by the end of post-autologous stem cell transplantation (post-ASCT) consolidation treatment were reported. Complete response (CR) is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (<) 5 percent (%) PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.
Time Frame From randomization to post-ASCT consolidation (after Cycle 6) before maintenance treatment (up to 10 months)

Outcome Measure Data

Analysis Population Description
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment. The outcome measure was planned to be reported for randomized participants only.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd)
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 97 99
Number (95% Confidence Interval) [Percentage of participants]
32.0
31.4%
42.4
42.8%
2. Secondary Outcome
Title Percentage of Participants With Overall Complete Response (CR)
Description Overall CR rate is defined as the percentage of participants who achieve CR, according to the IMWG criteria. CR is negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5% PCs in bone marrow.
Time Frame From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months)

Outcome Measure Data

Analysis Population Description
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 97 99 16
At the end of induction prior to ASCT
6.2
6.1%
7.1
7.2%
12.5
78.1%
At the end of ASCT prior to consolidation
5.2
5.1%
6.1
6.2%
12.5
78.1%
At the end of post-ASCT consolidation
10.3
10.1%
9.1
9.2%
12.5
78.1%
During maintenance phase
10.3
10.1%
13.1
13.2%
0
0%
3. Secondary Outcome
Title Percentage of Participants With Overall Stringent Complete Response (sCR)
Description Overall sCR rate is defined as the percentage of participants who achieved sCR, according to the IMWG criteria. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5 % PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.
Time Frame From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months)

Outcome Measure Data

Analysis Population Description
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 97 99 16
At the end of induction prior to ASCT
7.2
7.1%
12.1
12.2%
0
0%
At the end of ASCT prior to consolidation
14.4
14.1%
21.2
21.4%
43.8
273.8%
At the end of post-ASCT consolidation
32.0
31.4%
42.4
42.8%
56.3
351.9%
During maintenance phase
37.1
36.4%
49.5
50%
93.8
586.3%
4. Secondary Outcome
Title Percentage of Participants With Overall Response Rate (ORR)
Description ORR -percentage of participants who achieved partial response (PR) or better (PR, Very Good Partial Response [VGPR], CR or sCR) based on computerized algorithm as per IMWG criteria. PR -greater than or equal to (>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg//24 hours. If serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required. A >=50% reduction in the size of soft tissue plasmacytomas is also required; VGPR-serum and urine M-component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours; CR-negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. sCR- in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.
Time Frame From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months)

Outcome Measure Data

Analysis Population Description
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 97 99 16
At the end of induction prior to ASCT
91.8
90%
98.0
99%
100
625%
At the end of ASCT prior to consolidation
91.8
90%
99.0
100%
100
625%
At the end of post-ASCT consolidation
91.8
90%
99.0
100%
100
625%
During maintenance phase
91.8
90%
99.0
100%
100
625%
5. Secondary Outcome
Title Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better
Description VGPR or better rate is defined as the percentage of participants who achieved VGPR or better, according to the IMWG criteria. VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours.
Time Frame From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months)

Outcome Measure Data

Analysis Population Description
Population analyzed included response evaluable analysis set who achieved response (PR or better).
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 97 99 16
At the end of induction prior to ASCT
56.7
55.6%
71.7
72.4%
68.8
430%
At the end of ASCT prior to consolidation
66.0
64.7%
86.9
87.8%
100
625%
At the end of post-ASCT consolidation
73.2
71.8%
90.9
91.8%
100
625%
During maintenance phase
74.2
72.7%
91.9
92.8%
100
625%
6. Secondary Outcome
Title Percentage of Participants With Negative Minimal Residual Disease (MRD)
Description Minimal residual disease negative rate is defined as the percentage of participants who achieve MRD negative status by the respective time point. Minimal residual disease was evaluated in participants who achieved CR or sCR (including participants with VGPR or better and suspected daratumumab interference) using next-generation sequencing which utilizes multiple myeloma cell DNA from bone marrow aspirates at a threshold of less than (<) 10^5.
Time Frame From randomization to end of following: induction treatment, post-ASCT consolidation (after Cycle 6) (up to 4.5 months)

Outcome Measure Data

Analysis Population Description
Intent to treat (ITT) analysis set which included all randomized participants.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 103 104 16
MRD from randomization to prior to ASCT (10^5)
5.8
5.7%
19.2
19.4%
18.8
117.5%
Post ASCT consolidation (10^5)
14.6
14.3%
44.2
44.6%
50.0
312.5%
7. Secondary Outcome
Title Duration of Complete Response
Description Duration of CR is the duration from the date of initial documentation of a CR response, according to the IMWG criteria, to the date of first documented evidence of progressive disease (PR), or relapse from CR. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to [>=] 0.5 gram per deciliter [g/dL] and >=200 milligram [mg]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to Plasma cell (PC) proliferative disorder.
Time Frame From randomization to the date of first documented evidence of progressive disease or relapse from CR (up to 2 years and 5 months)

Outcome Measure Data

Analysis Population Description
Population analyzed included response evaluable analysis set who achieved response (PR or better).
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 89 98 16
Median (95% Confidence Interval) [Months]
NA
NA
NA
8. Secondary Outcome
Title Duration of Stringent Complete Response (sCR)
Description Duration of sCR is the duration from the date of initial documentation of a sCR response, according to the IMWG criteria, to the date of first documented evidence of progressive disease, or relapse from sCR. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Time Frame From randomization to the date of first documented evidence of progressive disease or relapse from sCR (up to 2 years and 5 months)

Outcome Measure Data

Analysis Population Description
Population analyzed included response evaluable analysis set who achieved response PR or better.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 89 98 16
Median (95% Confidence Interval) [Months]
NA
NA
NA
9. Secondary Outcome
Title Time to Stringent Complete Response (sCR)
Description Time to sCR is the duration from the date of randomization to the date of initial documentation of sCR, which was confirmed by a repeated measurement as required by the IMWG criteria.
Time Frame From randomization to the date of initial documentation of sCR (up to 2 years and 5 months)

Outcome Measure Data

Analysis Population Description
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 97 99 16
Median (95% Confidence Interval) [Months]
11.9
10.3
8.2
10. Secondary Outcome
Title Time to Complete Response or Better
Description Time to CR or better is the duration from the date of randomization to the date of initial documentation of CR or better, which was confirmed by a repeated measurement as required by the IMWG criteria.
Time Frame From randomization to the date of initial documentation of CR (Up to 2 years and 5 months)

Outcome Measure Data

Analysis Population Description
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 97 99 16
Median (95% Confidence Interval) [Months]
9.2
9.1
7.3
11. Secondary Outcome
Title Time to Very Good Partial Response (VGPR) or Better
Description Time to VGPR or better is the duration from the date of randomization to the date of initial documentation of VGPR or better, which was confirmed by a repeated measurement as required by the IMWG criteria.
Time Frame From randomization to the date of initial documentation of VGPR or better (up to 2 years and 5 months)

Outcome Measure Data

Analysis Population Description
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 97 99 16
Median (95% Confidence Interval) [Months]
3.0
2.2
2.1
12. Secondary Outcome
Title Time to Partial Response (PR) or Better
Description Time to PR or better is the duration from the date of randomization to the date of initial documentation of PR or better, which was confirmed by a repeated measurement as required by the IMWG criteria.
Time Frame From randomization to the date of initial documentation of PR or better (up to 2 years and 5 months)

Outcome Measure Data

Analysis Population Description
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 97 99 16
Median (95% Confidence Interval) [Months]
0.8
0.8
0.8
13. Secondary Outcome
Title Progression-free Survival (PFS)
Description PFS is defined as the duration from the date of randomization to the date of first documented evidence of progressive disease or death, whichever comes first. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Time Frame Up to 24 months

Outcome Measure Data

Analysis Population Description
ITT analysis set which included all randomized participants.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 103 104 16
Median (95% Confidence Interval) [Months]
NA
NA
NA
14. Secondary Outcome
Title Overall Survival (OS)
Description OS is measured from the date of randomization to the date of the participant's death.
Time Frame From randomization to the date of initial documentation of participant's death (up to 2 years and 5 months)

Outcome Measure Data

Analysis Population Description
ITT analysis set which included all randomized participants.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 103 104 16
Median (95% Confidence Interval) [Months]
NA
NA
NA
15. Secondary Outcome
Title Time to Progression (TTP)
Description TTP is defined as the duration from the date of randomization to the date of first documented evidence of progressive disease according to the IMWG criteria.
Time Frame From randomization to the date of first documented evidence of progressive disease (up to 2 years and 5 months)

Outcome Measure Data

Analysis Population Description
ITT analysis set which included all randomized participants.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 103 104 16
Median (95% Confidence Interval) [Months]
NA
NA
NA
16. Secondary Outcome
Title Duration of Response
Description Duration of response is defined as the duration from the date of initial documentation of a response (PR or better) according to the IMWG criteria to the date of first documented evidence of progressive disease according to the IMWG criteria. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Time Frame From the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive (up to 2 years and 5 months)

Outcome Measure Data

Analysis Population Description
ITT analysis set which included all randomized participants.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVd
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Measure Participants 103 104 16
Median (95% Confidence Interval) [Months]
NA
NA
NA

Adverse Events

Time Frame Up to 3 years and 5 months
Adverse Event Reporting Description 4 participants in D-RVd and 2 in RVd group were randomized but did not receive any treatment. 1 participant randomized to D-RVd group received RVd treatment and was counted in D-RVd group for ITT analysis and RVd group for safety analysis. So, safety analysis set included 99 participants in D-RVd and 102 in RVd group who received at least 1 dose of study treatment.
Arm/Group Title Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVD
Arm/Group Description Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
All Cause Mortality
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/102 (2.9%) 2/99 (2%) 1/16 (6.3%)
Serious Adverse Events
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 49/102 (48%) 35/99 (35.4%) 10/16 (62.5%)
Blood and lymphatic system disorders
Anaemia 2/102 (2%) 0/99 (0%) 0/16 (0%)
Febrile Neutropenia 0/102 (0%) 2/99 (2%) 2/16 (12.5%)
Neutropenia 0/102 (0%) 1/99 (1%) 0/16 (0%)
Cardiac disorders
Angina Pectoris 1/102 (1%) 0/99 (0%) 0/16 (0%)
Atrial Flutter 1/102 (1%) 1/99 (1%) 0/16 (0%)
Atrial Tachycardia 1/102 (1%) 0/99 (0%) 0/16 (0%)
Sinus Bradycardia 0/102 (0%) 1/99 (1%) 0/16 (0%)
Congenital, familial and genetic disorders
Sickle Cell Anaemia 1/102 (1%) 0/99 (0%) 0/16 (0%)
Gastrointestinal disorders
Abdominal Pain 1/102 (1%) 3/99 (3%) 0/16 (0%)
Abdominal Pain Upper 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Colitis 0/102 (0%) 1/99 (1%) 0/16 (0%)
Diarrhoea 1/102 (1%) 4/99 (4%) 0/16 (0%)
Haemorrhoidal Haemorrhage 1/102 (1%) 0/99 (0%) 0/16 (0%)
Intestinal Infarction 0/102 (0%) 1/99 (1%) 0/16 (0%)
Nausea 0/102 (0%) 2/99 (2%) 1/16 (6.3%)
Small Intestinal Obstruction 2/102 (2%) 0/99 (0%) 0/16 (0%)
Vomiting 0/102 (0%) 1/99 (1%) 1/16 (6.3%)
General disorders
Chills 1/102 (1%) 0/99 (0%) 0/16 (0%)
Localised Oedema 1/102 (1%) 0/99 (0%) 0/16 (0%)
Non-Cardiac Chest Pain 1/102 (1%) 0/99 (0%) 0/16 (0%)
Pyrexia 8/102 (7.8%) 9/99 (9.1%) 1/16 (6.3%)
Systemic Inflammatory Response Syndrome 1/102 (1%) 0/99 (0%) 0/16 (0%)
Immune system disorders
Hypersensitivity 1/102 (1%) 0/99 (0%) 0/16 (0%)
Serum Sickness-Like Reaction 1/102 (1%) 0/99 (0%) 0/16 (0%)
Infections and infestations
Aspergillus Infection 0/102 (0%) 1/99 (1%) 0/16 (0%)
Bacteraemia 1/102 (1%) 0/99 (0%) 0/16 (0%)
Bronchitis 1/102 (1%) 0/99 (0%) 0/16 (0%)
Escherichia Bacteraemia 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Gastroenteritis 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Gastroenteritis Escherichia Coli 0/102 (0%) 1/99 (1%) 0/16 (0%)
Influenza 5/102 (4.9%) 1/99 (1%) 0/16 (0%)
Lung Infection 1/102 (1%) 1/99 (1%) 0/16 (0%)
Pneumonia 8/102 (7.8%) 8/99 (8.1%) 4/16 (25%)
Pneumonia Bacterial 0/102 (0%) 1/99 (1%) 0/16 (0%)
Respiratory Syncytial Virus Bronchiolitis 0/102 (0%) 1/99 (1%) 0/16 (0%)
Respiratory Syncytial Virus Infection 0/102 (0%) 1/99 (1%) 0/16 (0%)
Sepsis 1/102 (1%) 3/99 (3%) 0/16 (0%)
Septic Shock 1/102 (1%) 0/99 (0%) 0/16 (0%)
Sinusitis 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Staphylococcal Infection 1/102 (1%) 0/99 (0%) 0/16 (0%)
Upper Respiratory Tract Infection 1/102 (1%) 1/99 (1%) 0/16 (0%)
Viral Infection 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Viral Upper Respiratory Tract Infection 0/102 (0%) 1/99 (1%) 0/16 (0%)
Injury, poisoning and procedural complications
Fibula Fracture 1/102 (1%) 0/99 (0%) 0/16 (0%)
Hip Fracture 1/102 (1%) 0/99 (0%) 0/16 (0%)
Spinal Compression Fracture 1/102 (1%) 0/99 (0%) 0/16 (0%)
Investigations
Blood Creatine Phosphokinase Increased 1/102 (1%) 0/99 (0%) 0/16 (0%)
Metabolism and nutrition disorders
Dehydration 3/102 (2.9%) 1/99 (1%) 0/16 (0%)
Gout 1/102 (1%) 0/99 (0%) 0/16 (0%)
Hyperkalaemia 1/102 (1%) 0/99 (0%) 0/16 (0%)
Hypokalaemia 0/102 (0%) 1/99 (1%) 0/16 (0%)
Hyponatraemia 0/102 (0%) 1/99 (1%) 0/16 (0%)
Tumour Lysis Syndrome 1/102 (1%) 0/99 (0%) 0/16 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 1/102 (1%) 0/99 (0%) 0/16 (0%)
Back Pain 2/102 (2%) 1/99 (1%) 0/16 (0%)
Bone Lesion 0/102 (0%) 1/99 (1%) 0/16 (0%)
Neck Pain 1/102 (1%) 0/99 (0%) 0/16 (0%)
Pain in Extremity 0/102 (0%) 1/99 (1%) 1/16 (6.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal Cell Carcinoma 0/102 (0%) 1/99 (1%) 0/16 (0%)
Squamous Cell Carcinoma of Skin 0/102 (0%) 2/99 (2%) 0/16 (0%)
Nervous system disorders
Headache 0/102 (0%) 2/99 (2%) 0/16 (0%)
Neuralgia 2/102 (2%) 0/99 (0%) 0/16 (0%)
Neuropathy Peripheral 1/102 (1%) 0/99 (0%) 0/16 (0%)
Peripheral Sensory Neuropathy 2/102 (2%) 1/99 (1%) 0/16 (0%)
Seizure 1/102 (1%) 1/99 (1%) 0/16 (0%)
Syncope 0/102 (0%) 2/99 (2%) 0/16 (0%)
Renal and urinary disorders
Acute Kidney Injury 4/102 (3.9%) 2/99 (2%) 0/16 (0%)
Bladder Perforation 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Reproductive system and breast disorders
Female Genital Tract Fistula 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Asthma 0/102 (0%) 1/99 (1%) 0/16 (0%)
Dyspnoea 4/102 (3.9%) 0/99 (0%) 0/16 (0%)
Pneumonitis 1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Pulmonary Embolism 4/102 (3.9%) 1/99 (1%) 0/16 (0%)
Pulmonary Oedema 1/102 (1%) 0/99 (0%) 0/16 (0%)
Skin and subcutaneous tissue disorders
Drug Reaction with Eosinophilia and Systemic Symptoms 2/102 (2%) 0/99 (0%) 0/16 (0%)
Hypersensitivity Vasculitis 1/102 (1%) 0/99 (0%) 0/16 (0%)
Surgical and medical procedures
Cholecystectomy 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Vascular disorders
Deep Vein Thrombosis 1/102 (1%) 1/99 (1%) 0/16 (0%)
Hypotension 1/102 (1%) 1/99 (1%) 0/16 (0%)
Thrombophlebitis Superficial 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Other (Not Including Serious) Adverse Events
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Randomized: Daratumumab+RVd (D-RVd) Safety Run-in: D-RVD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 102/102 (100%) 99/99 (100%) 16/16 (100%)
Blood and lymphatic system disorders
Anaemia 32/102 (31.4%) 32/99 (32.3%) 7/16 (43.8%)
Leukopenia 27/102 (26.5%) 34/99 (34.3%) 9/16 (56.3%)
Lymphopenia 29/102 (28.4%) 30/99 (30.3%) 13/16 (81.3%)
Monocytosis 0/102 (0%) 1/99 (1%) 2/16 (12.5%)
Neutropenia 32/102 (31.4%) 47/99 (47.5%) 12/16 (75%)
Thrombocytopenia 31/102 (30.4%) 43/99 (43.4%) 8/16 (50%)
Cardiac disorders
Palpitations 1/102 (1%) 5/99 (5.1%) 0/16 (0%)
Sinus Tachycardia 1/102 (1%) 2/99 (2%) 2/16 (12.5%)
Tachycardia 3/102 (2.9%) 3/99 (3%) 3/16 (18.8%)
Bradycardia 0/102 (0%) 2/99 (2%) 0/16 (0%)
Sinus Bradycardia 1/102 (1%) 2/99 (2%) 0/16 (0%)
Ear and labyrinth disorders
Ear Pain 0/102 (0%) 2/99 (2%) 1/16 (6.3%)
Tinnitus 4/102 (3.9%) 5/99 (5.1%) 1/16 (6.3%)
Vertigo 0/102 (0%) 3/99 (3%) 1/16 (6.3%)
Ear Congestion 1/102 (1%) 2/99 (2%) 0/16 (0%)
Ear Discomfort 0/102 (0%) 2/99 (2%) 0/16 (0%)
Hypoacusis 0/102 (0%) 2/99 (2%) 0/16 (0%)
Endocrine disorders
Adrenal Insufficiency 0/102 (0%) 1/99 (1%) 1/16 (6.3%)
Hypothyroidism 1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Eye disorders
Dry Eye 2/102 (2%) 4/99 (4%) 0/16 (0%)
Eye Irritation 3/102 (2.9%) 1/99 (1%) 0/16 (0%)
Lacrimation Increased 2/102 (2%) 4/99 (4%) 1/16 (6.3%)
Vision Blurred 13/102 (12.7%) 16/99 (16.2%) 1/16 (6.3%)
Cataract 1/102 (1%) 1/99 (1%) 1/16 (6.3%)
Visual Impairment 2/102 (2%) 2/99 (2%) 0/16 (0%)
Gastrointestinal disorders
Abdominal Distension 4/102 (3.9%) 5/99 (5.1%) 3/16 (18.8%)
Abdominal Pain 9/102 (8.8%) 21/99 (21.2%) 4/16 (25%)
Abdominal Pain Upper 2/102 (2%) 5/99 (5.1%) 1/16 (6.3%)
Constipation 41/102 (40.2%) 46/99 (46.5%) 8/16 (50%)
Diarrhoea 43/102 (42.2%) 51/99 (51.5%) 8/16 (50%)
Dry Mouth 4/102 (3.9%) 7/99 (7.1%) 1/16 (6.3%)
Dyspepsia 8/102 (7.8%) 13/99 (13.1%) 0/16 (0%)
Flatulence 0/102 (0%) 3/99 (3%) 0/16 (0%)
Gastrooesophageal Reflux Disease 2/102 (2%) 9/99 (9.1%) 1/16 (6.3%)
Haemorrhoids 2/102 (2%) 2/99 (2%) 1/16 (6.3%)
Nausea 47/102 (46.1%) 45/99 (45.5%) 5/16 (31.3%)
Stomatitis 4/102 (3.9%) 2/99 (2%) 3/16 (18.8%)
Toothache 1/102 (1%) 4/99 (4%) 0/16 (0%)
Vomiting 24/102 (23.5%) 27/99 (27.3%) 5/16 (31.3%)
Abdominal Pain Lower 2/102 (2%) 2/99 (2%) 0/16 (0%)
Dental Caries 0/102 (0%) 2/99 (2%) 0/16 (0%)
Dysphagia 0/102 (0%) 2/99 (2%) 0/16 (0%)
Food Poisoning 0/102 (0%) 1/99 (1%) 1/16 (6.3%)
Haemorrhoidal Haemorrhage 2/102 (2%) 0/99 (0%) 1/16 (6.3%)
Oral Dysaesthesia 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
General disorders
Asthenia 9/102 (8.8%) 3/99 (3%) 1/16 (6.3%)
Chest Discomfort 3/102 (2.9%) 8/99 (8.1%) 0/16 (0%)
Chills 8/102 (7.8%) 22/99 (22.2%) 4/16 (25%)
Face Oedema 1/102 (1%) 3/99 (3%) 2/16 (12.5%)
Fatigue 56/102 (54.9%) 61/99 (61.6%) 9/16 (56.3%)
Gait Disturbance 3/102 (2.9%) 2/99 (2%) 0/16 (0%)
Influenza Like Illness 5/102 (4.9%) 12/99 (12.1%) 0/16 (0%)
Injection Site Erythema 1/102 (1%) 4/99 (4%) 0/16 (0%)
Injection Site Rash 5/102 (4.9%) 4/99 (4%) 1/16 (6.3%)
Injection Site Reaction 4/102 (3.9%) 3/99 (3%) 0/16 (0%)
Localised Oedema 2/102 (2%) 4/99 (4%) 0/16 (0%)
Malaise 1/102 (1%) 3/99 (3%) 2/16 (12.5%)
Non-Cardiac Chest Pain 7/102 (6.9%) 6/99 (6.1%) 2/16 (12.5%)
Oedema 7/102 (6.9%) 4/99 (4%) 1/16 (6.3%)
Oedema Peripheral 35/102 (34.3%) 32/99 (32.3%) 6/16 (37.5%)
Pain 5/102 (4.9%) 8/99 (8.1%) 1/16 (6.3%)
Peripheral Swelling 3/102 (2.9%) 8/99 (8.1%) 1/16 (6.3%)
Pyrexia 20/102 (19.6%) 33/99 (33.3%) 6/16 (37.5%)
Injection Site Pruritus 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Swelling 0/102 (0%) 1/99 (1%) 1/16 (6.3%)
Hepatobiliary disorders
Hyperbilirubinaemia 3/102 (2.9%) 2/99 (2%) 2/16 (12.5%)
Cholelithiasis 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Immune system disorders
Hypersensitivity 0/102 (0%) 2/99 (2%) 1/16 (6.3%)
Hypogammaglobulinaemia 0/102 (0%) 2/99 (2%) 3/16 (18.8%)
Seasonal Allergy 2/102 (2%) 3/99 (3%) 0/16 (0%)
Infections and infestations
Bronchitis 1/102 (1%) 2/99 (2%) 2/16 (12.5%)
Cellulitis 3/102 (2.9%) 1/99 (1%) 1/16 (6.3%)
Ear Infection 0/102 (0%) 1/99 (1%) 2/16 (12.5%)
Gastroenteritis Viral 1/102 (1%) 1/99 (1%) 2/16 (12.5%)
Hordeolum 3/102 (2.9%) 4/99 (4%) 0/16 (0%)
Influenza 4/102 (3.9%) 4/99 (4%) 1/16 (6.3%)
Lung Infection 1/102 (1%) 2/99 (2%) 1/16 (6.3%)
Nasopharyngitis 3/102 (2.9%) 7/99 (7.1%) 1/16 (6.3%)
Otitis Media 0/102 (0%) 4/99 (4%) 0/16 (0%)
Parainfluenzae Virus Infection 2/102 (2%) 5/99 (5.1%) 1/16 (6.3%)
Pneumonia 2/102 (2%) 5/99 (5.1%) 2/16 (12.5%)
Rhinovirus Infection 2/102 (2%) 5/99 (5.1%) 0/16 (0%)
Sinusitis 2/102 (2%) 6/99 (6.1%) 2/16 (12.5%)
Tooth Infection 1/102 (1%) 2/99 (2%) 1/16 (6.3%)
Upper Respiratory Tract Infection 37/102 (36.3%) 46/99 (46.5%) 8/16 (50%)
Urinary Tract Infection 3/102 (2.9%) 2/99 (2%) 1/16 (6.3%)
Viral Upper Respiratory Tract Infection 4/102 (3.9%) 3/99 (3%) 0/16 (0%)
Acute Sinusitis 1/102 (1%) 2/99 (2%) 0/16 (0%)
Anal Tinea 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Diverticulitis 1/102 (1%) 1/99 (1%) 1/16 (6.3%)
Eye Infection 1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Gastrointestinal Infection 0/102 (0%) 2/99 (2%) 0/16 (0%)
Herpes Zoster 0/102 (0%) 2/99 (2%) 0/16 (0%)
Laryngitis 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Metapneumovirus Infection 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Pneumonia Influenzal 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Respiratory Syncytial Virus Infection 2/102 (2%) 2/99 (2%) 0/16 (0%)
Skin Infection 1/102 (1%) 2/99 (2%) 0/16 (0%)
Staphylococcal Infection 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Subcutaneous Abscess 0/102 (0%) 2/99 (2%) 0/16 (0%)
Viral Infection 0/102 (0%) 1/99 (1%) 1/16 (6.3%)
Injury, poisoning and procedural complications
Contusion 7/102 (6.9%) 8/99 (8.1%) 0/16 (0%)
Fall 9/102 (8.8%) 4/99 (4%) 1/16 (6.3%)
Infusion Related Reaction 0/102 (0%) 3/99 (3%) 0/16 (0%)
Procedural Pain 0/102 (0%) 3/99 (3%) 0/16 (0%)
Spinal Fracture 3/102 (2.9%) 0/99 (0%) 0/16 (0%)
Tooth Fracture 0/102 (0%) 3/99 (3%) 0/16 (0%)
Vascular Access Site Swelling 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Investigations
Alanine Aminotransferase Increased 15/102 (14.7%) 13/99 (13.1%) 1/16 (6.3%)
Aspartate Aminotransferase Increased 14/102 (13.7%) 10/99 (10.1%) 2/16 (12.5%)
Blood Alkaline Phosphatase Increased 9/102 (8.8%) 8/99 (8.1%) 1/16 (6.3%)
Blood Creatinine Increased 7/102 (6.9%) 6/99 (6.1%) 0/16 (0%)
Weight Decreased 4/102 (3.9%) 9/99 (9.1%) 0/16 (0%)
Weight Increased 2/102 (2%) 3/99 (3%) 0/16 (0%)
Adjusted Calcium 1/102 (1%) 1/99 (1%) 1/16 (6.3%)
Gamma-Glutamyltransferase Increased 0/102 (0%) 2/99 (2%) 0/16 (0%)
Metabolism and nutrition disorders
Decreased Appetite 11/102 (10.8%) 21/99 (21.2%) 2/16 (12.5%)
Dehydration 2/102 (2%) 3/99 (3%) 0/16 (0%)
Hypercalcaemia 4/102 (3.9%) 1/99 (1%) 1/16 (6.3%)
Hyperglycaemia 20/102 (19.6%) 9/99 (9.1%) 2/16 (12.5%)
Hyperkalaemia 2/102 (2%) 4/99 (4%) 0/16 (0%)
Hypermagnesaemia 3/102 (2.9%) 2/99 (2%) 0/16 (0%)
Hypernatraemia 3/102 (2.9%) 1/99 (1%) 0/16 (0%)
Hyperuricaemia 7/102 (6.9%) 4/99 (4%) 0/16 (0%)
Hypoalbuminaemia 9/102 (8.8%) 11/99 (11.1%) 4/16 (25%)
Hypocalcaemia 14/102 (13.7%) 13/99 (13.1%) 8/16 (50%)
Hypoglycaemia 4/102 (3.9%) 3/99 (3%) 1/16 (6.3%)
Hypokalaemia 21/102 (20.6%) 20/99 (20.2%) 6/16 (37.5%)
Hypomagnesaemia 8/102 (7.8%) 3/99 (3%) 5/16 (31.3%)
Hyponatraemia 11/102 (10.8%) 14/99 (14.1%) 3/16 (18.8%)
Hypophosphataemia 12/102 (11.8%) 9/99 (9.1%) 5/16 (31.3%)
Hypercholesterolaemia 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Hyperphosphataemia 2/102 (2%) 2/99 (2%) 0/16 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 29/102 (28.4%) 24/99 (24.2%) 3/16 (18.8%)
Arthritis 3/102 (2.9%) 0/99 (0%) 0/16 (0%)
Back Pain 27/102 (26.5%) 32/99 (32.3%) 5/16 (31.3%)
Bone Pain 6/102 (5.9%) 11/99 (11.1%) 0/16 (0%)
Flank Pain 3/102 (2.9%) 1/99 (1%) 0/16 (0%)
Joint Swelling 0/102 (0%) 3/99 (3%) 0/16 (0%)
Limb Discomfort 3/102 (2.9%) 0/99 (0%) 0/16 (0%)
Muscle Spasms 15/102 (14.7%) 18/99 (18.2%) 2/16 (12.5%)
Muscular Weakness 13/102 (12.7%) 7/99 (7.1%) 1/16 (6.3%)
Musculoskeletal Chest Pain 9/102 (8.8%) 11/99 (11.1%) 1/16 (6.3%)
Musculoskeletal Pain 6/102 (5.9%) 5/99 (5.1%) 3/16 (18.8%)
Musculoskeletal Stiffness 1/102 (1%) 3/99 (3%) 0/16 (0%)
Myalgia 17/102 (16.7%) 20/99 (20.2%) 2/16 (12.5%)
Neck Pain 1/102 (1%) 5/99 (5.1%) 0/16 (0%)
Pain in Extremity 16/102 (15.7%) 14/99 (14.1%) 5/16 (31.3%)
Kyphosis 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Osteonecrosis of Jaw 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Squamous Cell Carcinoma 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Uterine Leiomyoma 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Nervous system disorders
Cognitive Disorder 1/102 (1%) 3/99 (3%) 0/16 (0%)
Disturbance in Attention 1/102 (1%) 3/99 (3%) 0/16 (0%)
Dizziness 22/102 (21.6%) 17/99 (17.2%) 2/16 (12.5%)
Dizziness Postural 1/102 (1%) 3/99 (3%) 0/16 (0%)
Dysgeusia 22/102 (21.6%) 23/99 (23.2%) 2/16 (12.5%)
Headache 19/102 (18.6%) 25/99 (25.3%) 1/16 (6.3%)
Hypoaesthesia 6/102 (5.9%) 5/99 (5.1%) 0/16 (0%)
Memory Impairment 6/102 (5.9%) 1/99 (1%) 0/16 (0%)
Neuralgia 9/102 (8.8%) 10/99 (10.1%) 1/16 (6.3%)
Neuropathy Peripheral 41/102 (40.2%) 24/99 (24.2%) 2/16 (12.5%)
Paraesthesia 10/102 (9.8%) 20/99 (20.2%) 3/16 (18.8%)
Peripheral Sensory Neuropathy 37/102 (36.3%) 35/99 (35.4%) 6/16 (37.5%)
Presyncope 3/102 (2.9%) 2/99 (2%) 0/16 (0%)
Syncope 3/102 (2.9%) 4/99 (4%) 0/16 (0%)
Tremor 8/102 (7.8%) 10/99 (10.1%) 2/16 (12.5%)
Hyperaesthesia 0/102 (0%) 2/99 (2%) 0/16 (0%)
Peripheral Motor Neuropathy 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Restless Legs Syndrome 0/102 (0%) 2/99 (2%) 0/16 (0%)
Sinus Headache 1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Somnolence 1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Psychiatric disorders
Anxiety 12/102 (11.8%) 12/99 (12.1%) 3/16 (18.8%)
Confusional State 1/102 (1%) 2/99 (2%) 1/16 (6.3%)
Depression 5/102 (4.9%) 6/99 (6.1%) 1/16 (6.3%)
Insomnia 30/102 (29.4%) 39/99 (39.4%) 6/16 (37.5%)
Agitation 1/102 (1%) 2/99 (2%) 0/16 (0%)
Libido Decreased 1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Restlessness 2/102 (2%) 2/99 (2%) 0/16 (0%)
Renal and urinary disorders
Dysuria 5/102 (4.9%) 4/99 (4%) 0/16 (0%)
Pollakiuria 1/102 (1%) 2/99 (2%) 0/16 (0%)
Polyuria 0/102 (0%) 2/99 (2%) 0/16 (0%)
Proteinuria 1/102 (1%) 1/99 (1%) 1/16 (6.3%)
Reproductive system and breast disorders
Erectile Dysfunction 2/102 (2%) 2/99 (2%) 1/16 (6.3%)
Vulvovaginal Pruritus 1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough 25/102 (24.5%) 38/99 (38.4%) 9/16 (56.3%)
Dysphonia 2/102 (2%) 4/99 (4%) 1/16 (6.3%)
Dyspnoea 29/102 (28.4%) 22/99 (22.2%) 3/16 (18.8%)
Dyspnoea Exertional 2/102 (2%) 5/99 (5.1%) 0/16 (0%)
Epistaxis 7/102 (6.9%) 4/99 (4%) 0/16 (0%)
Hiccups 3/102 (2.9%) 2/99 (2%) 1/16 (6.3%)
Nasal Congestion 12/102 (11.8%) 18/99 (18.2%) 4/16 (25%)
Oropharyngeal Pain 9/102 (8.8%) 6/99 (6.1%) 2/16 (12.5%)
Rhinitis Allergic 2/102 (2%) 5/99 (5.1%) 1/16 (6.3%)
Rhinorrhoea 1/102 (1%) 5/99 (5.1%) 0/16 (0%)
Sinus Congestion 3/102 (2.9%) 4/99 (4%) 0/16 (0%)
Throat Irritation 0/102 (0%) 6/99 (6.1%) 0/16 (0%)
Upper-Airway Cough Syndrome 0/102 (0%) 3/99 (3%) 1/16 (6.3%)
Productive Cough 2/102 (2%) 1/99 (1%) 1/16 (6.3%)
Respiratory Alkalosis 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Sneezing 0/102 (0%) 2/99 (2%) 0/16 (0%)
Wheezing 1/102 (1%) 1/99 (1%) 1/16 (6.3%)
Skin and subcutaneous tissue disorders
Alopecia 5/102 (4.9%) 5/99 (5.1%) 1/16 (6.3%)
Dry Skin 9/102 (8.8%) 9/99 (9.1%) 0/16 (0%)
Erythema 4/102 (3.9%) 3/99 (3%) 0/16 (0%)
Hyperhidrosis 5/102 (4.9%) 2/99 (2%) 2/16 (12.5%)
Night Sweats 4/102 (3.9%) 1/99 (1%) 0/16 (0%)
Pruritus 10/102 (9.8%) 13/99 (13.1%) 1/16 (6.3%)
Pruritus Generalised 0/102 (0%) 3/99 (3%) 0/16 (0%)
Rash 24/102 (23.5%) 19/99 (19.2%) 4/16 (25%)
Rash Maculo-Papular 24/102 (23.5%) 20/99 (20.2%) 2/16 (12.5%)
Urticaria 3/102 (2.9%) 5/99 (5.1%) 0/16 (0%)
Actinic Keratosis 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Ecchymosis 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Ingrowing Nail 0/102 (0%) 2/99 (2%) 0/16 (0%)
Rash Generalised 2/102 (2%) 2/99 (2%) 0/16 (0%)
Rash Pruritic 2/102 (2%) 2/99 (2%) 0/16 (0%)
Skin Mass 0/102 (0%) 2/99 (2%) 0/16 (0%)
Swelling Face 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Vascular disorders
Deep Vein Thrombosis 5/102 (4.9%) 1/99 (1%) 0/16 (0%)
Flushing 2/102 (2%) 8/99 (8.1%) 2/16 (12.5%)
Hot Flush 5/102 (4.9%) 5/99 (5.1%) 0/16 (0%)
Hypertension 9/102 (8.8%) 10/99 (10.1%) 3/16 (18.8%)
Hypotension 13/102 (12.7%) 9/99 (9.1%) 1/16 (6.3%)
Orthostatic Hypotension 3/102 (2.9%) 5/99 (5.1%) 0/16 (0%)
Lymphoedema 0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Orthostatic Hypertension 0/102 (0%) 0/99 (0%) 1/16 (6.3%)

Limitations/Caveats

Initial protocol did not require MRD testing in all participants, impacting the interpretation of MRD negativity rates in ITT group, which strongly favored daratumumab treatment. Longer follow-up time is needed to determine this.

More Information

Certain Agreements

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

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.

Results Point of Contact

Name/Title Clinical Leader
Organization Janssen Research & Development, LLC
Phone 844-434-4210
Email ClinicalTrialDisclosure@its.jnj.com
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02874742
Other Study ID Numbers:
  • CR108195
  • 54767414MMY2004
First Posted:
Aug 22, 2016
Last Update Posted:
Jun 7, 2022
Last Verified:
May 1, 2022