Trial Outcomes & Findings for Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma (NCT NCT02874742)

Last Updated: 2025-02-04

Results Overview

Percentage of participants who had 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 plasma cells (PCs) by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

224 participants

Primary outcome timeframe

From randomization to post-ASCT consolidation (after Cycle 6) before maintenance treatment (up to 10 months)

Results posted on

2025-02-04

Participant Flow

223 participants were enrolled/randomized (16 in safety run-in,104 to D-RVd and 103 to RVd group). 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).

Participant was a screen-failure but was mistakenly randomized first to D-RVd ; 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.

Participant milestones

Participant milestones
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Overall Study STARTED	103	104	16
Overall Study Treated (Safety Analysis Set)	101	100	16
Overall Study COMPLETED	76	88	15
Overall Study NOT COMPLETED	27	16	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Overall Study Death	0	1	0
Overall Study Lost to Follow-up	5	4	1
Overall Study Withdrawal by Subject	17	8	0
Overall Study Other	4	1	0
Overall Study Progressive Disease	1	0	0
Overall Study Screen Failure	0	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=103 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=104 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were 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 n=223 Participants Total of all reporting groups
Age, Continuous	59 years STANDARD_DEVIATION 7.27 • n=5 Participants	57.2 years STANDARD_DEVIATION 9.79 • n=7 Participants	59.8 years STANDARD_DEVIATION 5.96 • n=5 Participants	58.2 years STANDARD_DEVIATION 8.49 • n=4 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	46 Participants n=7 Participants	8 Participants n=5 Participants	97 Participants n=4 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	58 Participants n=7 Participants	8 Participants n=5 Participants	126 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	18 Participants n=5 Participants	14 Participants n=7 Participants	4 Participants n=5 Participants	36 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	76 Participants n=5 Participants	85 Participants n=7 Participants	11 Participants n=5 Participants	172 Participants n=4 Participants
Race/Ethnicity, Customized More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Unknown or Not Reported	5 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment UNITED STATES	103 Participants n=5 Participants	104 Participants n=7 Participants	16 Participants n=5 Participants	223 Participants n=4 Participants

PRIMARY outcome

Timeframe: From randomization to post-ASCT consolidation (after Cycle 6) before maintenance treatment (up to 10 months)

Population: 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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=97 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=99 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Percentage of Participants With Stringent Complete Response (sCR)	32.0 Percentage of participants Interval 22.9 to 42.2	42.4 Percentage of participants Interval 32.5 to 52.8	—

SECONDARY outcome

Timeframe: From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance period of 24 months (overall duration up to 34 months)

Population: 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. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants analyzed at each specified timepoints.

CR or better rate is defined as the percentage of participants who achieve CR or sCR, 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. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry. For 2 participants (1 in each randomized treatment group), data were updated by the study sites which resulted in their inclusion to the response-evaluable analysis set after the primary analysis.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=98 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=100 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Percentage of Participants With Complete Response (CR) or Better At the end of induction prior to ASCT	13.4 Percentage of participants Interval 7.3 to 21.8	19.2 Percentage of participants Interval 12.0 to 28.3	12.5 Percentage of participants Interval 1.6 to 38.3
Percentage of Participants With Complete Response (CR) or Better At the end of ASCT prior to consolidation	19.6 Percentage of participants Interval 12.2 to 28.9	27.3 Percentage of participants Interval 18.8 to 37.1	56.3 Percentage of participants Interval 29.9 to 80.2
Percentage of Participants With Complete Response (CR) or Better At the end of post-ASCT consolidation	42.3 Percentage of participants Interval 32.3 to 52.7	51.5 Percentage of participants Interval 41.3 to 61.7	68.8 Percentage of participants Interval 41.3 to 89.0
Percentage of Participants With Complete Response (CR) or Better At the end of maintenance period (up to 24 Months)	60.2 Percentage of participants Interval 49.8 to 70.0	83.0 Percentage of participants Interval 74.2 to 89.8	93.8 Percentage of participants Interval 69.8 to 99.8

SECONDARY outcome

Timeframe: From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance treatment of 24 months (overall duration up to 34 months)

Population: 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. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants analyzed at each specified timepoints.

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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=98 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=100 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Percentage of Participants With Overall Stringent Complete Response (sCR) At the end of induction prior to ASCT	7.2 Percentage of participants Interval 3.0 to 14.3	12.1 Percentage of participants Interval 6.4 to 20.2	0 Percentage of participants Here NA signifies that 95% CI was not estimable as zero participant had events during at the end of induction prior to ASCT.
Percentage of Participants With Overall Stringent Complete Response (sCR) At the end of ASCT prior to consolidation	14.4 Percentage of participants Interval 8.1 to 23.0	21.2 Percentage of participants Interval 13.6 to 30.6	43.8 Percentage of participants Interval 19.8 to 70.1
Percentage of Participants With Overall Stringent Complete Response (sCR) At the end of post-ASCT consolidation	32.0 Percentage of participants Interval 22.9 to 42.2	42.4 Percentage of participants Interval 32.5 to 52.8	56.3 Percentage of participants Interval 29.9 to 80.2
Percentage of Participants With Overall Stringent Complete Response (sCR) At the end of Maintenance Treatment (up to 24 Months)	48.0 Percentage of participants Interval 37.8 to 58.3	67.0 Percentage of participants Interval 56.9 to 76.1	93.8 Percentage of participants Interval 69.8 to 99.8

SECONDARY outcome

Population: 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. Here, 'n' (number analyzed) signifies number of participants analyzed at each specified timepoints.

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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=98 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=100 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Percentage of Participants With Overall Response Rate (ORR) At the end of induction prior to ASCT	91.8 Percentage of participants Interval 84.4 to 96.4	98.0 Percentage of participants Interval 92.9 to 99.8	100 Percentage of participants Interval 79.4 to 100.0
Percentage of Participants With Overall Response Rate (ORR) At the end of ASCT prior to consolidation	91.8 Percentage of participants Interval 84.4 to 96.4	99.0 Percentage of participants Interval 94.5 to 100.0	100 Percentage of participants Interval 79.4 to 100.0
Percentage of Participants With Overall Response Rate (ORR) At the end of post-ASCT consolidation	91.8 Percentage of participants Interval 84.4 to 96.4	99.0 Percentage of participants Interval 94.5 to 100.0	100 Percentage of participants Interval 79.4 to 100.0
Percentage of Participants With Overall Response Rate (ORR) At the End of Maintenance Treatment (up to 24 Months)	91.8 Percentage of participants Interval 84.5 to 96.4	99.0 Percentage of participants Interval 94.6 to 100.0	100.0 Percentage of participants Interval 79.4 to 100.0

SECONDARY outcome

Population: Population analyzed included response evaluable analysis set who achieved response (PR or better). Here, 'n' (number analyzed) signifies number of participants analyzed at each specified timepoints.

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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=98 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=100 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better At the end of induction prior to ASCT	56.7 Percentage of participants Interval 46.3 to 66.7	71.7 Percentage of participants Interval 61.8 to 80.3	68.8 Percentage of participants Interval 41.3 to 89.0
Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better At the end of ASCT prior to consolidation	66.0 Percentage of participants Interval 55.7 to 75.3	86.9 Percentage of participants Interval 78.6 to 92.8	100 Percentage of participants Interval 79.4 to 100.0
Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better At the end of post-ASCT consolidation	73.2 Percentage of participants Interval 63.2 to 81.7	90.9 Percentage of participants Interval 83.4 to 95.8	100 Percentage of participants Interval 79.4 to 100.0
Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better At the End of Maintenance Period (up to 24 Months)	77.6 Percentage of participants Interval 68.0 to 85.4	96.0 Percentage of participants Interval 90.1 to 98.9	100.0 Percentage of participants Interval 79.4 to 100.0

SECONDARY outcome

Timeframe: From randomization to end of following: induction treatment, post-ASCT consolidation (after Cycle 6) (up to 4.5 months), and at the end of maintenance period of 24 months (overall duration up to 34 months)

Population: Intent to treat (ITT) analysis set which included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=103 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=104 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Percentage of Participants With Negative Minimal Residual Disease (MRD) MRD from randomization to prior to ASCT (10^5)	7.8 Percentage of participants Interval 3.4 to 14.7	22.1 Percentage of participants Interval 14.6 to 31.3	18.8 Percentage of participants Interval 4.0 to 45.6
Percentage of Participants With Negative Minimal Residual Disease (MRD) Post ASCT consolidation (10^5)	20.4 Percentage of participants Interval 13.1 to 29.5	50.0 Percentage of participants Interval 40.0 to 60.0	50.0 Percentage of participants Interval 24.7 to 75.3
Percentage of Participants With Negative Minimal Residual Disease (MRD) At the End of Maintenance Period (up to 24 Months) (10^5)	30.1 Percentage of participants Interval 21.5 to 39.9	64.4 Percentage of participants Interval 54.4 to 73.6	81.3 Percentage of participants Interval 54.4 to 96.0

SECONDARY outcome

Timeframe: From randomization to the date of first documented evidence of progressive disease or relapse from CR (up to 5 years)

Population: Population analyzed included response evaluable analysis set who achieved response (PR or better).

Duration of CR or better is the duration from the date of initial documentation of a CR or sCR 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 milligrams \[mg\]/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 cells (PCs) proliferative disorder.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=90 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=99 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Duration of Complete Response or Better	NA Months Here NA signifies that Median and 95% CI was not estimable due to insufficient number of events.	NA Months Here NA signifies that Median and 95% CI was not estimable due to insufficient number of events.	NA Months Here NA signifies that Median and 95% CI was not estimable due to insufficient number of events.

SECONDARY outcome

Timeframe: From randomization to the date of first documented evidence of progressive disease or relapse from sCR (up to 5 years)

Population: Population analyzed included response evaluable analysis set who achieved response PR or better.

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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=90 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=99 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Duration of Stringent Complete Response (sCR)	NA Months Here NA signifies Median and 95% CI was not estimable due to an insufficient number of events.	NA Months Here NA signifies Median and 95% CI was not estimable due to an insufficient number of events.	NA Months Interval 42.4 to Here NA signifies Median and 95% CI was not estimable due to an insufficient number of events.

SECONDARY outcome

Timeframe: From randomization to the date of initial documentation of sCR (up to 5 years)

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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=98 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=100 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Time to Stringent Complete Response (sCR)	14.3 Months Interval 9.2 to 21.7	10.2 Months Interval 8.8 to 13.0	8.4 Months Interval 7.1 to 15.2

SECONDARY outcome

Timeframe: From randomization to the date of initial documentation of CR (up to 5 years)

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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=98 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=100 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Time to Complete Response or Better	9.6 Months Interval 8.4 to 12.2	8.9 Months Interval 7.9 to 9.4	7.7 Months Interval 6.7 to 9.7

SECONDARY outcome

Timeframe: From randomization to the date of initial documentation of VGPR or better (up to 5 years)

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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=98 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=100 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Time to Very Good Partial Response (VGPR) or Better	3.0 Months Interval 2.2 to 6.3	2.2 Months Interval 2.1 to 2.7	2.1 Months Interval 0.9 to 6.7

SECONDARY outcome

Timeframe: From randomization to the date of initial documentation of PR or better (up to 5 years)

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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=98 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=100 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Time to Partial Response (PR) or Better	0.8 Months Interval 0.8 to 1.0	0.8 Months Interval 0.8 to 0.8	0.8 Months Interval 0.7 to 1.4

SECONDARY outcome

Timeframe: From randomization to the date of first documented evidence of progressive disease or death (up to 5 years)

Population: ITT analysis set which included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=103 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=104 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Progression-free Survival (PFS)	NA Months Here NA signifies that Median and 95% CI was not estimable due to insufficient number of events.	NA Months Here NA signifies that Median and 95% CI was not estimable due to insufficient number of events.	NA Months Interval 57.6 to Here NA signifies that Median and upper limit of 95% CI was not estimable due to insufficient number of events.

SECONDARY outcome

Timeframe: From randomization to the date of initial documentation of participant's death (up to 5 years)

Population: ITT analysis set which included all randomized participants.

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

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=103 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=104 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Overall Survival (OS)	NA Months Here NA signifies that Median and 95% CI was not estimable due to insufficient number of events.	NA Months Here NA signifies that Median and 95% CI was not estimable due to insufficient number of events.	NA Months Here NA signifies that Median and 95% CI was not estimable due to insufficient number of events.

SECONDARY outcome

Timeframe: From randomization to the date of first documented evidence of progressive disease (up to 5 years)

Population: ITT analysis set which included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=103 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=104 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Time to Progression (TTP)	NA Months Here NA signifies that Median and 95% CI was not estimable due to insufficient number of events.	NA Months Here NA signifies that Median and 95% CI was not estimable due to insufficient number of events.	NA Months Interval 57.59 to Here NA signifies that Median and upper limit of 95% CI was not estimable due to insufficient number of events.

SECONDARY outcome

Timeframe: From the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive (up to 5 years)

Population: Population analyzed included response evaluable analysis set who achieved response PR or better.

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.

Outcome measures

Outcome measures
Measure	Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) n=90 Participants Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy \[HDT\] and autologous stem cell transplantation \[ASCT\]; 6-week consolidation phase)- participants received lenalidomide 25 milligrams (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 mg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.	Randomized: Daratumumab+RVd (D-RVd) n=99 Participants 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 milligrams 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. Per protocol amendment 4, to provide flexibility and prioritize safety during the global coronavirus-19 (COVID-19) pandemic, participants were given the option to switch from daratumumab IV to daratumumab SC at the discretion of the investigator.	Safety Run-in: D-RVd n=16 Participants 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/kg 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. After 2 years of maintenance therapy, participants could continue to lenalidomide monotherapy per standard of care. Long-term follow-up phase- all participants were followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study.
Duration of Response	NA Months Here NA signifies that Median and 95% CI was not estimable due to insufficient number of events.	NA Months Here NA signifies that Median and 95% CI was not estimable due to insufficient number of events.	NA Months Interval 56.8 to Here NA signifies that Median and upper limit of 95% CI was not estimable due to insufficient number of events.

Adverse Events

Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd)

Serious events: 53 serious events

Other events: 102 other events

Deaths: 7 deaths

Randomized: Daratumumab+RVd (D-RVd)

Serious events: 46 serious events

Other events: 99 other events

Deaths: 7 deaths

Safety Run-in: D-RVd

Serious events: 12 serious events

Other events: 16 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Leader

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER