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
Active, not recruiting
CT.gov ID
NCT02874742
Collaborator
(none)
224
Enrollment
36
Locations
2
Arms
69
Anticipated Duration (Months)
6.2
Patients Per Site
0.1
Patients Per Site Per Month

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.

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 1, 2016
Actual Primary Completion Date :
Jan 1, 2019
Anticipated Study Completion Date :
May 1, 2022

Arms and Interventions

ArmIntervention/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

SiteCityStateCountryPostal Code
1BirminghamAlabamaUnited States
2DuarteCaliforniaUnited States
3La JollaCaliforniaUnited States
4Los AngelesCaliforniaUnited States
5San FranciscoCaliforniaUnited States
6AuroraColoradoUnited States
7WashingtonDistrict of ColumbiaUnited States
8OrlandoFloridaUnited States
9TampaFloridaUnited States
10AtlantaGeorgiaUnited States
11ChicagoIllinoisUnited States
12WestwoodKansasUnited States
13New OrleansLouisianaUnited States
14BaltimoreMarylandUnited States
15BostonMassachusettsUnited States
16WorcesterMassachusettsUnited States
17DetroitMichiganUnited States
18Saint LouisMissouriUnited States
19OmahaNebraskaUnited States
20BuffaloNew YorkUnited States
21New YorkNew YorkUnited States
22Chapel HillNorth CarolinaUnited States
23CharlotteNorth CarolinaUnited States
24DurhamNorth CarolinaUnited States
25Winston-SalemNorth CarolinaUnited States
26ColumbusOhioUnited States
27PortlandOregonUnited States
28AbingtonPennsylvaniaUnited States
29PhiladelphiaPennsylvaniaUnited States
30NashvilleTennesseeUnited States
31DallasTexasUnited States
32HoustonTexasUnited States
33Salt Lake CityUtahUnited States
34SeattleWashingtonUnited States
35SpokaneWashingtonUnited States
36MilwaukeeWisconsinUnited 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:
Oct 8, 2021
Last Verified:
Oct 1, 2021
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details223 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 DetailParticipant 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVD
Arm/Group DescriptionInduction 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
STARTED10310416
Safety1029916
COMPLETED000
NOT COMPLETED10310416

Baseline Characteristics

Arm/Group TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVDTotal
Arm/Group DescriptionInduction 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 Participants1029916217
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
TitlePercentage of Participants With Stringent Complete Response (sCR)
DescriptionPercentage 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)
Arm/Group DescriptionInduction 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 Participants9799
Number (95% Confidence Interval) [Percentage of participants]
32.0
31.4%
42.4
42.8%
2. Secondary Outcome
TitlePercentage of Participants With Overall Complete Response (CR)
DescriptionOverall 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants979916
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
TitlePercentage of Participants With Overall Stringent Complete Response (sCR)
DescriptionOverall 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants979916
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
TitlePercentage of Participants With Overall Response Rate (ORR)
DescriptionORR -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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants979916
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
TitlePercentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better
DescriptionVGPR 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants979916
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
TitlePercentage of Participants With Negative Minimal Residual Disease (MRD)
DescriptionMinimal 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants10310416
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
TitleDuration of Complete Response
DescriptionDuration 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants899816
Median (95% Confidence Interval) [Months]
NA
NA
NA
8. Secondary Outcome
TitleDuration of Stringent Complete Response (sCR)
DescriptionDuration 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants899816
Median (95% Confidence Interval) [Months]
NA
NA
NA
9. Secondary Outcome
TitleTime to Stringent Complete Response (sCR)
DescriptionTime 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants979916
Median (95% Confidence Interval) [Months]
11.9
10.3
8.2
10. Secondary Outcome
TitleTime to Complete Response or Better
DescriptionTime 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants979916
Median (95% Confidence Interval) [Months]
9.2
9.1
7.3
11. Secondary Outcome
TitleTime to Very Good Partial Response (VGPR) or Better
DescriptionTime 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants979916
Median (95% Confidence Interval) [Months]
3.0
2.2
2.1
12. Secondary Outcome
TitleTime to Partial Response (PR) or Better
DescriptionTime 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants979916
Median (95% Confidence Interval) [Months]
0.8
0.8
0.8
13. Secondary Outcome
TitleProgression-free Survival (PFS)
DescriptionPFS 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 FrameUp to 24 months

Outcome Measure Data

Analysis Population Description
ITT analysis set which included all randomized participants.
Arm/Group TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants10310416
Median (95% Confidence Interval) [Months]
NA
NA
NA
14. Secondary Outcome
TitleOverall Survival (OS)
DescriptionOS is measured from the date of randomization to the date of the participant's death.
Time FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants10310416
Median (95% Confidence Interval) [Months]
NA
NA
NA
15. Secondary Outcome
TitleTime to Progression (TTP)
DescriptionTTP 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants10310416
Median (95% Confidence Interval) [Months]
NA
NA
NA
16. Secondary Outcome
TitleDuration of Response
DescriptionDuration 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 FrameFrom 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVd
Arm/Group DescriptionInduction 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 Participants10310416
Median (95% Confidence Interval) [Months]
NA
NA
NA

Adverse Events

Time FrameUp 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 TitleRandomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)Randomized: Daratumumab+RVd (D-RVd)Safety Run-in: D-RVD
Arm/Group DescriptionInduction 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 (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total3/102 (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 (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total49/102 (48%) 35/99 (35.4%) 10/16 (62.5%)
Blood and lymphatic system disorders
Anaemia2/102 (2%) 0/99 (0%) 0/16 (0%)
Febrile Neutropenia0/102 (0%) 2/99 (2%) 2/16 (12.5%)
Neutropenia0/102 (0%) 1/99 (1%) 0/16 (0%)
Cardiac disorders
Angina Pectoris1/102 (1%) 0/99 (0%) 0/16 (0%)
Atrial Flutter1/102 (1%) 1/99 (1%) 0/16 (0%)
Atrial Tachycardia1/102 (1%) 0/99 (0%) 0/16 (0%)
Sinus Bradycardia0/102 (0%) 1/99 (1%) 0/16 (0%)
Congenital, familial and genetic disorders
Sickle Cell Anaemia1/102 (1%) 0/99 (0%) 0/16 (0%)
Gastrointestinal disorders
Abdominal Pain1/102 (1%) 3/99 (3%) 0/16 (0%)
Abdominal Pain Upper0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Colitis0/102 (0%) 1/99 (1%) 0/16 (0%)
Diarrhoea1/102 (1%) 4/99 (4%) 0/16 (0%)
Haemorrhoidal Haemorrhage1/102 (1%) 0/99 (0%) 0/16 (0%)
Intestinal Infarction0/102 (0%) 1/99 (1%) 0/16 (0%)
Nausea0/102 (0%) 2/99 (2%) 1/16 (6.3%)
Small Intestinal Obstruction2/102 (2%) 0/99 (0%) 0/16 (0%)
Vomiting0/102 (0%) 1/99 (1%) 1/16 (6.3%)
General disorders
Chills1/102 (1%) 0/99 (0%) 0/16 (0%)
Localised Oedema1/102 (1%) 0/99 (0%) 0/16 (0%)
Non-Cardiac Chest Pain1/102 (1%) 0/99 (0%) 0/16 (0%)
Pyrexia8/102 (7.8%) 9/99 (9.1%) 1/16 (6.3%)
Systemic Inflammatory Response Syndrome1/102 (1%) 0/99 (0%) 0/16 (0%)
Immune system disorders
Hypersensitivity1/102 (1%) 0/99 (0%) 0/16 (0%)
Serum Sickness-Like Reaction1/102 (1%) 0/99 (0%) 0/16 (0%)
Infections and infestations
Aspergillus Infection0/102 (0%) 1/99 (1%) 0/16 (0%)
Bacteraemia1/102 (1%) 0/99 (0%) 0/16 (0%)
Bronchitis1/102 (1%) 0/99 (0%) 0/16 (0%)
Escherichia Bacteraemia0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Gastroenteritis0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Gastroenteritis Escherichia Coli0/102 (0%) 1/99 (1%) 0/16 (0%)
Influenza5/102 (4.9%) 1/99 (1%) 0/16 (0%)
Lung Infection1/102 (1%) 1/99 (1%) 0/16 (0%)
Pneumonia8/102 (7.8%) 8/99 (8.1%) 4/16 (25%)
Pneumonia Bacterial0/102 (0%) 1/99 (1%) 0/16 (0%)
Respiratory Syncytial Virus Bronchiolitis0/102 (0%) 1/99 (1%) 0/16 (0%)
Respiratory Syncytial Virus Infection0/102 (0%) 1/99 (1%) 0/16 (0%)
Sepsis1/102 (1%) 3/99 (3%) 0/16 (0%)
Septic Shock1/102 (1%) 0/99 (0%) 0/16 (0%)
Sinusitis0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Staphylococcal Infection1/102 (1%) 0/99 (0%) 0/16 (0%)
Upper Respiratory Tract Infection1/102 (1%) 1/99 (1%) 0/16 (0%)
Viral Infection0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Viral Upper Respiratory Tract Infection0/102 (0%) 1/99 (1%) 0/16 (0%)
Injury, poisoning and procedural complications
Fibula Fracture1/102 (1%) 0/99 (0%) 0/16 (0%)
Hip Fracture1/102 (1%) 0/99 (0%) 0/16 (0%)
Spinal Compression Fracture1/102 (1%) 0/99 (0%) 0/16 (0%)
Investigations
Blood Creatine Phosphokinase Increased1/102 (1%) 0/99 (0%) 0/16 (0%)
Metabolism and nutrition disorders
Dehydration3/102 (2.9%) 1/99 (1%) 0/16 (0%)
Gout1/102 (1%) 0/99 (0%) 0/16 (0%)
Hyperkalaemia1/102 (1%) 0/99 (0%) 0/16 (0%)
Hypokalaemia0/102 (0%) 1/99 (1%) 0/16 (0%)
Hyponatraemia0/102 (0%) 1/99 (1%) 0/16 (0%)
Tumour Lysis Syndrome1/102 (1%) 0/99 (0%) 0/16 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia1/102 (1%) 0/99 (0%) 0/16 (0%)
Back Pain2/102 (2%) 1/99 (1%) 0/16 (0%)
Bone Lesion0/102 (0%) 1/99 (1%) 0/16 (0%)
Neck Pain1/102 (1%) 0/99 (0%) 0/16 (0%)
Pain in Extremity0/102 (0%) 1/99 (1%) 1/16 (6.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal Cell Carcinoma0/102 (0%) 1/99 (1%) 0/16 (0%)
Squamous Cell Carcinoma of Skin0/102 (0%) 2/99 (2%) 0/16 (0%)
Nervous system disorders
Headache0/102 (0%) 2/99 (2%) 0/16 (0%)
Neuralgia2/102 (2%) 0/99 (0%) 0/16 (0%)
Neuropathy Peripheral1/102 (1%) 0/99 (0%) 0/16 (0%)
Peripheral Sensory Neuropathy2/102 (2%) 1/99 (1%) 0/16 (0%)
Seizure1/102 (1%) 1/99 (1%) 0/16 (0%)
Syncope0/102 (0%) 2/99 (2%) 0/16 (0%)
Renal and urinary disorders
Acute Kidney Injury4/102 (3.9%) 2/99 (2%) 0/16 (0%)
Bladder Perforation0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Reproductive system and breast disorders
Female Genital Tract Fistula0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Asthma0/102 (0%) 1/99 (1%) 0/16 (0%)
Dyspnoea4/102 (3.9%) 0/99 (0%) 0/16 (0%)
Pneumonitis1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Pulmonary Embolism4/102 (3.9%) 1/99 (1%) 0/16 (0%)
Pulmonary Oedema1/102 (1%) 0/99 (0%) 0/16 (0%)
Skin and subcutaneous tissue disorders
Drug Reaction with Eosinophilia and Systemic Symptoms2/102 (2%) 0/99 (0%) 0/16 (0%)
Hypersensitivity Vasculitis1/102 (1%) 0/99 (0%) 0/16 (0%)
Surgical and medical procedures
Cholecystectomy0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Vascular disorders
Deep Vein Thrombosis1/102 (1%) 1/99 (1%) 0/16 (0%)
Hypotension1/102 (1%) 1/99 (1%) 0/16 (0%)
Thrombophlebitis Superficial0/102 (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 (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total102/102 (100%) 99/99 (100%) 16/16 (100%)
Blood and lymphatic system disorders
Anaemia32/102 (31.4%) 32/99 (32.3%) 7/16 (43.8%)
Leukopenia27/102 (26.5%) 34/99 (34.3%) 9/16 (56.3%)
Lymphopenia29/102 (28.4%) 30/99 (30.3%) 13/16 (81.3%)
Monocytosis0/102 (0%) 1/99 (1%) 2/16 (12.5%)
Neutropenia32/102 (31.4%) 47/99 (47.5%) 12/16 (75%)
Thrombocytopenia31/102 (30.4%) 43/99 (43.4%) 8/16 (50%)
Cardiac disorders
Palpitations1/102 (1%) 5/99 (5.1%) 0/16 (0%)
Sinus Tachycardia1/102 (1%) 2/99 (2%) 2/16 (12.5%)
Tachycardia3/102 (2.9%) 3/99 (3%) 3/16 (18.8%)
Bradycardia0/102 (0%) 2/99 (2%) 0/16 (0%)
Sinus Bradycardia1/102 (1%) 2/99 (2%) 0/16 (0%)
Ear and labyrinth disorders
Ear Pain0/102 (0%) 2/99 (2%) 1/16 (6.3%)
Tinnitus4/102 (3.9%) 5/99 (5.1%) 1/16 (6.3%)
Vertigo0/102 (0%) 3/99 (3%) 1/16 (6.3%)
Ear Congestion1/102 (1%) 2/99 (2%) 0/16 (0%)
Ear Discomfort0/102 (0%) 2/99 (2%) 0/16 (0%)
Hypoacusis0/102 (0%) 2/99 (2%) 0/16 (0%)
Endocrine disorders
Adrenal Insufficiency0/102 (0%) 1/99 (1%) 1/16 (6.3%)
Hypothyroidism1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Eye disorders
Dry Eye2/102 (2%) 4/99 (4%) 0/16 (0%)
Eye Irritation3/102 (2.9%) 1/99 (1%) 0/16 (0%)
Lacrimation Increased2/102 (2%) 4/99 (4%) 1/16 (6.3%)
Vision Blurred13/102 (12.7%) 16/99 (16.2%) 1/16 (6.3%)
Cataract1/102 (1%) 1/99 (1%) 1/16 (6.3%)
Visual Impairment2/102 (2%) 2/99 (2%) 0/16 (0%)
Gastrointestinal disorders
Abdominal Distension4/102 (3.9%) 5/99 (5.1%) 3/16 (18.8%)
Abdominal Pain9/102 (8.8%) 21/99 (21.2%) 4/16 (25%)
Abdominal Pain Upper2/102 (2%) 5/99 (5.1%) 1/16 (6.3%)
Constipation41/102 (40.2%) 46/99 (46.5%) 8/16 (50%)
Diarrhoea43/102 (42.2%) 51/99 (51.5%) 8/16 (50%)
Dry Mouth4/102 (3.9%) 7/99 (7.1%) 1/16 (6.3%)
Dyspepsia8/102 (7.8%) 13/99 (13.1%) 0/16 (0%)
Flatulence0/102 (0%) 3/99 (3%) 0/16 (0%)
Gastrooesophageal Reflux Disease2/102 (2%) 9/99 (9.1%) 1/16 (6.3%)
Haemorrhoids2/102 (2%) 2/99 (2%) 1/16 (6.3%)
Nausea47/102 (46.1%) 45/99 (45.5%) 5/16 (31.3%)
Stomatitis4/102 (3.9%) 2/99 (2%) 3/16 (18.8%)
Toothache1/102 (1%) 4/99 (4%) 0/16 (0%)
Vomiting24/102 (23.5%) 27/99 (27.3%) 5/16 (31.3%)
Abdominal Pain Lower2/102 (2%) 2/99 (2%) 0/16 (0%)
Dental Caries0/102 (0%) 2/99 (2%) 0/16 (0%)
Dysphagia0/102 (0%) 2/99 (2%) 0/16 (0%)
Food Poisoning0/102 (0%) 1/99 (1%) 1/16 (6.3%)
Haemorrhoidal Haemorrhage2/102 (2%) 0/99 (0%) 1/16 (6.3%)
Oral Dysaesthesia0/102 (0%) 0/99 (0%) 1/16 (6.3%)
General disorders
Asthenia9/102 (8.8%) 3/99 (3%) 1/16 (6.3%)
Chest Discomfort3/102 (2.9%) 8/99 (8.1%) 0/16 (0%)
Chills8/102 (7.8%) 22/99 (22.2%) 4/16 (25%)
Face Oedema1/102 (1%) 3/99 (3%) 2/16 (12.5%)
Fatigue56/102 (54.9%) 61/99 (61.6%) 9/16 (56.3%)
Gait Disturbance3/102 (2.9%) 2/99 (2%) 0/16 (0%)
Influenza Like Illness5/102 (4.9%) 12/99 (12.1%) 0/16 (0%)
Injection Site Erythema1/102 (1%) 4/99 (4%) 0/16 (0%)
Injection Site Rash5/102 (4.9%) 4/99 (4%) 1/16 (6.3%)
Injection Site Reaction4/102 (3.9%) 3/99 (3%) 0/16 (0%)
Localised Oedema2/102 (2%) 4/99 (4%) 0/16 (0%)
Malaise1/102 (1%) 3/99 (3%) 2/16 (12.5%)
Non-Cardiac Chest Pain7/102 (6.9%) 6/99 (6.1%) 2/16 (12.5%)
Oedema7/102 (6.9%) 4/99 (4%) 1/16 (6.3%)
Oedema Peripheral35/102 (34.3%) 32/99 (32.3%) 6/16 (37.5%)
Pain5/102 (4.9%) 8/99 (8.1%) 1/16 (6.3%)
Peripheral Swelling3/102 (2.9%) 8/99 (8.1%) 1/16 (6.3%)
Pyrexia20/102 (19.6%) 33/99 (33.3%) 6/16 (37.5%)
Injection Site Pruritus0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Swelling0/102 (0%) 1/99 (1%) 1/16 (6.3%)
Hepatobiliary disorders
Hyperbilirubinaemia3/102 (2.9%) 2/99 (2%) 2/16 (12.5%)
Cholelithiasis0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Immune system disorders
Hypersensitivity0/102 (0%) 2/99 (2%) 1/16 (6.3%)
Hypogammaglobulinaemia0/102 (0%) 2/99 (2%) 3/16 (18.8%)
Seasonal Allergy2/102 (2%) 3/99 (3%) 0/16 (0%)
Infections and infestations
Bronchitis1/102 (1%) 2/99 (2%) 2/16 (12.5%)
Cellulitis3/102 (2.9%) 1/99 (1%) 1/16 (6.3%)
Ear Infection0/102 (0%) 1/99 (1%) 2/16 (12.5%)
Gastroenteritis Viral1/102 (1%) 1/99 (1%) 2/16 (12.5%)
Hordeolum3/102 (2.9%) 4/99 (4%) 0/16 (0%)
Influenza4/102 (3.9%) 4/99 (4%) 1/16 (6.3%)
Lung Infection1/102 (1%) 2/99 (2%) 1/16 (6.3%)
Nasopharyngitis3/102 (2.9%) 7/99 (7.1%) 1/16 (6.3%)
Otitis Media0/102 (0%) 4/99 (4%) 0/16 (0%)
Parainfluenzae Virus Infection2/102 (2%) 5/99 (5.1%) 1/16 (6.3%)
Pneumonia2/102 (2%) 5/99 (5.1%) 2/16 (12.5%)
Rhinovirus Infection2/102 (2%) 5/99 (5.1%) 0/16 (0%)
Sinusitis2/102 (2%) 6/99 (6.1%) 2/16 (12.5%)
Tooth Infection1/102 (1%) 2/99 (2%) 1/16 (6.3%)
Upper Respiratory Tract Infection37/102 (36.3%) 46/99 (46.5%) 8/16 (50%)
Urinary Tract Infection3/102 (2.9%) 2/99 (2%) 1/16 (6.3%)
Viral Upper Respiratory Tract Infection4/102 (3.9%) 3/99 (3%) 0/16 (0%)
Acute Sinusitis1/102 (1%) 2/99 (2%) 0/16 (0%)
Anal Tinea0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Diverticulitis1/102 (1%) 1/99 (1%) 1/16 (6.3%)
Eye Infection1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Gastrointestinal Infection0/102 (0%) 2/99 (2%) 0/16 (0%)
Herpes Zoster0/102 (0%) 2/99 (2%) 0/16 (0%)
Laryngitis0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Metapneumovirus Infection0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Pneumonia Influenzal0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Respiratory Syncytial Virus Infection2/102 (2%) 2/99 (2%) 0/16 (0%)
Skin Infection1/102 (1%) 2/99 (2%) 0/16 (0%)
Staphylococcal Infection0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Subcutaneous Abscess0/102 (0%) 2/99 (2%) 0/16 (0%)
Viral Infection0/102 (0%) 1/99 (1%) 1/16 (6.3%)
Injury, poisoning and procedural complications
Contusion7/102 (6.9%) 8/99 (8.1%) 0/16 (0%)
Fall9/102 (8.8%) 4/99 (4%) 1/16 (6.3%)
Infusion Related Reaction0/102 (0%) 3/99 (3%) 0/16 (0%)
Procedural Pain0/102 (0%) 3/99 (3%) 0/16 (0%)
Spinal Fracture3/102 (2.9%) 0/99 (0%) 0/16 (0%)
Tooth Fracture0/102 (0%) 3/99 (3%) 0/16 (0%)
Vascular Access Site Swelling0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Investigations
Alanine Aminotransferase Increased15/102 (14.7%) 13/99 (13.1%) 1/16 (6.3%)
Aspartate Aminotransferase Increased14/102 (13.7%) 10/99 (10.1%) 2/16 (12.5%)
Blood Alkaline Phosphatase Increased9/102 (8.8%) 8/99 (8.1%) 1/16 (6.3%)
Blood Creatinine Increased7/102 (6.9%) 6/99 (6.1%) 0/16 (0%)
Weight Decreased4/102 (3.9%) 9/99 (9.1%) 0/16 (0%)
Weight Increased2/102 (2%) 3/99 (3%) 0/16 (0%)
Adjusted Calcium1/102 (1%) 1/99 (1%) 1/16 (6.3%)
Gamma-Glutamyltransferase Increased0/102 (0%) 2/99 (2%) 0/16 (0%)
Metabolism and nutrition disorders
Decreased Appetite11/102 (10.8%) 21/99 (21.2%) 2/16 (12.5%)
Dehydration2/102 (2%) 3/99 (3%) 0/16 (0%)
Hypercalcaemia4/102 (3.9%) 1/99 (1%) 1/16 (6.3%)
Hyperglycaemia20/102 (19.6%) 9/99 (9.1%) 2/16 (12.5%)
Hyperkalaemia2/102 (2%) 4/99 (4%) 0/16 (0%)
Hypermagnesaemia3/102 (2.9%) 2/99 (2%) 0/16 (0%)
Hypernatraemia3/102 (2.9%) 1/99 (1%) 0/16 (0%)
Hyperuricaemia7/102 (6.9%) 4/99 (4%) 0/16 (0%)
Hypoalbuminaemia9/102 (8.8%) 11/99 (11.1%) 4/16 (25%)
Hypocalcaemia14/102 (13.7%) 13/99 (13.1%) 8/16 (50%)
Hypoglycaemia4/102 (3.9%) 3/99 (3%) 1/16 (6.3%)
Hypokalaemia21/102 (20.6%) 20/99 (20.2%) 6/16 (37.5%)
Hypomagnesaemia8/102 (7.8%) 3/99 (3%) 5/16 (31.3%)
Hyponatraemia11/102 (10.8%) 14/99 (14.1%) 3/16 (18.8%)
Hypophosphataemia12/102 (11.8%) 9/99 (9.1%) 5/16 (31.3%)
Hypercholesterolaemia0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Hyperphosphataemia2/102 (2%) 2/99 (2%) 0/16 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia29/102 (28.4%) 24/99 (24.2%) 3/16 (18.8%)
Arthritis3/102 (2.9%) 0/99 (0%) 0/16 (0%)
Back Pain27/102 (26.5%) 32/99 (32.3%) 5/16 (31.3%)
Bone Pain6/102 (5.9%) 11/99 (11.1%) 0/16 (0%)
Flank Pain3/102 (2.9%) 1/99 (1%) 0/16 (0%)
Joint Swelling0/102 (0%) 3/99 (3%) 0/16 (0%)
Limb Discomfort3/102 (2.9%) 0/99 (0%) 0/16 (0%)
Muscle Spasms15/102 (14.7%) 18/99 (18.2%) 2/16 (12.5%)
Muscular Weakness13/102 (12.7%) 7/99 (7.1%) 1/16 (6.3%)
Musculoskeletal Chest Pain9/102 (8.8%) 11/99 (11.1%) 1/16 (6.3%)
Musculoskeletal Pain6/102 (5.9%) 5/99 (5.1%) 3/16 (18.8%)
Musculoskeletal Stiffness1/102 (1%) 3/99 (3%) 0/16 (0%)
Myalgia17/102 (16.7%) 20/99 (20.2%) 2/16 (12.5%)
Neck Pain1/102 (1%) 5/99 (5.1%) 0/16 (0%)
Pain in Extremity16/102 (15.7%) 14/99 (14.1%) 5/16 (31.3%)
Kyphosis0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Osteonecrosis of Jaw0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Squamous Cell Carcinoma0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Uterine Leiomyoma0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Nervous system disorders
Cognitive Disorder1/102 (1%) 3/99 (3%) 0/16 (0%)
Disturbance in Attention1/102 (1%) 3/99 (3%) 0/16 (0%)
Dizziness22/102 (21.6%) 17/99 (17.2%) 2/16 (12.5%)
Dizziness Postural1/102 (1%) 3/99 (3%) 0/16 (0%)
Dysgeusia22/102 (21.6%) 23/99 (23.2%) 2/16 (12.5%)
Headache19/102 (18.6%) 25/99 (25.3%) 1/16 (6.3%)
Hypoaesthesia6/102 (5.9%) 5/99 (5.1%) 0/16 (0%)
Memory Impairment6/102 (5.9%) 1/99 (1%) 0/16 (0%)
Neuralgia9/102 (8.8%) 10/99 (10.1%) 1/16 (6.3%)
Neuropathy Peripheral41/102 (40.2%) 24/99 (24.2%) 2/16 (12.5%)
Paraesthesia10/102 (9.8%) 20/99 (20.2%) 3/16 (18.8%)
Peripheral Sensory Neuropathy37/102 (36.3%) 35/99 (35.4%) 6/16 (37.5%)
Presyncope3/102 (2.9%) 2/99 (2%) 0/16 (0%)
Syncope3/102 (2.9%) 4/99 (4%) 0/16 (0%)
Tremor8/102 (7.8%) 10/99 (10.1%) 2/16 (12.5%)
Hyperaesthesia0/102 (0%) 2/99 (2%) 0/16 (0%)
Peripheral Motor Neuropathy0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Restless Legs Syndrome0/102 (0%) 2/99 (2%) 0/16 (0%)
Sinus Headache1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Somnolence1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Psychiatric disorders
Anxiety12/102 (11.8%) 12/99 (12.1%) 3/16 (18.8%)
Confusional State1/102 (1%) 2/99 (2%) 1/16 (6.3%)
Depression5/102 (4.9%) 6/99 (6.1%) 1/16 (6.3%)
Insomnia30/102 (29.4%) 39/99 (39.4%) 6/16 (37.5%)
Agitation1/102 (1%) 2/99 (2%) 0/16 (0%)
Libido Decreased1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Restlessness2/102 (2%) 2/99 (2%) 0/16 (0%)
Renal and urinary disorders
Dysuria5/102 (4.9%) 4/99 (4%) 0/16 (0%)
Pollakiuria1/102 (1%) 2/99 (2%) 0/16 (0%)
Polyuria0/102 (0%) 2/99 (2%) 0/16 (0%)
Proteinuria1/102 (1%) 1/99 (1%) 1/16 (6.3%)
Reproductive system and breast disorders
Erectile Dysfunction2/102 (2%) 2/99 (2%) 1/16 (6.3%)
Vulvovaginal Pruritus1/102 (1%) 0/99 (0%) 1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough25/102 (24.5%) 38/99 (38.4%) 9/16 (56.3%)
Dysphonia2/102 (2%) 4/99 (4%) 1/16 (6.3%)
Dyspnoea29/102 (28.4%) 22/99 (22.2%) 3/16 (18.8%)
Dyspnoea Exertional2/102 (2%) 5/99 (5.1%) 0/16 (0%)
Epistaxis7/102 (6.9%) 4/99 (4%) 0/16 (0%)
Hiccups3/102 (2.9%) 2/99 (2%) 1/16 (6.3%)
Nasal Congestion12/102 (11.8%) 18/99 (18.2%) 4/16 (25%)
Oropharyngeal Pain9/102 (8.8%) 6/99 (6.1%) 2/16 (12.5%)
Rhinitis Allergic2/102 (2%) 5/99 (5.1%) 1/16 (6.3%)
Rhinorrhoea1/102 (1%) 5/99 (5.1%) 0/16 (0%)
Sinus Congestion3/102 (2.9%) 4/99 (4%) 0/16 (0%)
Throat Irritation0/102 (0%) 6/99 (6.1%) 0/16 (0%)
Upper-Airway Cough Syndrome0/102 (0%) 3/99 (3%) 1/16 (6.3%)
Productive Cough2/102 (2%) 1/99 (1%) 1/16 (6.3%)
Respiratory Alkalosis0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Sneezing0/102 (0%) 2/99 (2%) 0/16 (0%)
Wheezing1/102 (1%) 1/99 (1%) 1/16 (6.3%)
Skin and subcutaneous tissue disorders
Alopecia5/102 (4.9%) 5/99 (5.1%) 1/16 (6.3%)
Dry Skin9/102 (8.8%) 9/99 (9.1%) 0/16 (0%)
Erythema4/102 (3.9%) 3/99 (3%) 0/16 (0%)
Hyperhidrosis5/102 (4.9%) 2/99 (2%) 2/16 (12.5%)
Night Sweats4/102 (3.9%) 1/99 (1%) 0/16 (0%)
Pruritus10/102 (9.8%) 13/99 (13.1%) 1/16 (6.3%)
Pruritus Generalised0/102 (0%) 3/99 (3%) 0/16 (0%)
Rash24/102 (23.5%) 19/99 (19.2%) 4/16 (25%)
Rash Maculo-Papular24/102 (23.5%) 20/99 (20.2%) 2/16 (12.5%)
Urticaria3/102 (2.9%) 5/99 (5.1%) 0/16 (0%)
Actinic Keratosis0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Ecchymosis0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Ingrowing Nail0/102 (0%) 2/99 (2%) 0/16 (0%)
Rash Generalised2/102 (2%) 2/99 (2%) 0/16 (0%)
Rash Pruritic2/102 (2%) 2/99 (2%) 0/16 (0%)
Skin Mass0/102 (0%) 2/99 (2%) 0/16 (0%)
Swelling Face0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Vascular disorders
Deep Vein Thrombosis5/102 (4.9%) 1/99 (1%) 0/16 (0%)
Flushing2/102 (2%) 8/99 (8.1%) 2/16 (12.5%)
Hot Flush5/102 (4.9%) 5/99 (5.1%) 0/16 (0%)
Hypertension9/102 (8.8%) 10/99 (10.1%) 3/16 (18.8%)
Hypotension13/102 (12.7%) 9/99 (9.1%) 1/16 (6.3%)
Orthostatic Hypotension3/102 (2.9%) 5/99 (5.1%) 0/16 (0%)
Lymphoedema0/102 (0%) 0/99 (0%) 1/16 (6.3%)
Orthostatic Hypertension0/102 (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/TitleClinical Leader
OrganizationJanssen Research & Development, LLC
Phone844-434-4210
EmailClinicalTrialDisclosure@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:
Oct 8, 2021
Last Verified:
Oct 1, 2021