Trial Outcomes & Findings for A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens (NCT NCT03412565)

Last Updated: 2025-04-29

Results Overview

ORR was defined as the percentage of participants who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria. IMWG criteria for PR: greater than or equal to (\>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to less than (\<) 200 milligrams (mg) per 24 hours, If the serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>=30%. In addition to the above criteria, if present at baseline, a \>=50% reduction in the size of soft tissue plasmacytomas is also required.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

265 participants

Primary outcome timeframe

Up to 2 years 3 months

Results posted on

2025-04-29

Participant Flow

Participant milestones

Participant milestones
Measure	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) Participants received daratumumab 1800 milligrams (mg) as a subcutaneous (SC) injection on Days 1, 8 and 15 of Cycles 1 to 3 (each cycle of 21 days) and on Day 1 of Cycle 4; bortezomib 1.3 milligrams per square meter (mg/m\^2) SC injection on Days 1, 4, 8 and 11 of Cycles 1 to 4; lenalidomide 25 mg orally on Day 1 through Day 14 of Cycles 1 to 4 and dexamethasone 20 mg orally or intravenously (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4.	D + Bortezomib + Melphalan + Prednisone (D-VMP) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
Overall Study STARTED	67	67	65	66
Overall Study COMPLETED	66	19	14	15
Overall Study NOT COMPLETED	1	48	51	51

Reasons for withdrawal

Reasons for withdrawal
Measure	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) Participants received daratumumab 1800 milligrams (mg) as a subcutaneous (SC) injection on Days 1, 8 and 15 of Cycles 1 to 3 (each cycle of 21 days) and on Day 1 of Cycle 4; bortezomib 1.3 milligrams per square meter (mg/m\^2) SC injection on Days 1, 4, 8 and 11 of Cycles 1 to 4; lenalidomide 25 mg orally on Day 1 through Day 14 of Cycles 1 to 4 and dexamethasone 20 mg orally or intravenously (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4.	D + Bortezomib + Melphalan + Prednisone (D-VMP) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
Overall Study Lost to Follow-up	0	0	1	0
Overall Study Physician Decision	0	0	0	1
Overall Study Withdrawal by Subject	0	4	5	5
Overall Study Death	1	3	4	5
Overall Study Data collection ended	0	41	41	40

Baseline Characteristics

A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) n=67 Participants Participants received daratumumab 1800 milligrams (mg) as a subcutaneous (SC) injection on Days 1, 8 and 15 of Cycles 1 to 3 (each cycle of 21 days) and on Day 1 of Cycle 4; bortezomib 1.3 milligrams per square meter (mg/m\^2) SC injection on Days 1, 4, 8 and 11 of Cycles 1 to 4; lenalidomide 25 mg orally on Day 1 through Day 14 of Cycles 1 to 4 and dexamethasone 20 mg orally or intravenously (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4.	D + Bortezomib + Melphalan + Prednisone (D-VMP) n=67 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) n=65 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=66 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Total n=265 Participants Total of all reporting groups
Age, Continuous	57.3 years STANDARD_DEVIATION 9.47 • n=39 Participants	74.9 years STANDARD_DEVIATION 4.54 • n=41 Participants	66.8 years STANDARD_DEVIATION 9.58 • n=35 Participants	61 years STANDARD_DEVIATION 9.77 • n=31 Participants	65 years STANDARD_DEVIATION 10.87 • n=146 Participants
Sex: Female, Male Female	19 Participants n=39 Participants	36 Participants n=41 Participants	20 Participants n=35 Participants	32 Participants n=31 Participants	107 Participants n=146 Participants
Sex: Female, Male Male	48 Participants n=39 Participants	31 Participants n=41 Participants	45 Participants n=35 Participants	34 Participants n=31 Participants	158 Participants n=146 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=39 Participants	6 Participants n=41 Participants	0 Participants n=35 Participants	7 Participants n=31 Participants	16 Participants n=146 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=39 Participants	39 Participants n=41 Participants	45 Participants n=35 Participants	43 Participants n=31 Participants	161 Participants n=146 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	30 Participants n=39 Participants	22 Participants n=41 Participants	20 Participants n=35 Participants	16 Participants n=31 Participants	88 Participants n=146 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants	0 Participants n=146 Participants
Race (NIH/OMB) Asian	0 Participants n=39 Participants	5 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants	5 Participants n=146 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants	0 Participants n=146 Participants
Race (NIH/OMB) Black or African American	5 Participants n=39 Participants	1 Participants n=41 Participants	2 Participants n=35 Participants	2 Participants n=31 Participants	10 Participants n=146 Participants
Race (NIH/OMB) White	38 Participants n=39 Participants	46 Participants n=41 Participants	45 Participants n=35 Participants	48 Participants n=31 Participants	177 Participants n=146 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants	0 Participants n=146 Participants
Race (NIH/OMB) Unknown or Not Reported	24 Participants n=39 Participants	15 Participants n=41 Participants	18 Participants n=35 Participants	16 Participants n=31 Participants	73 Participants n=146 Participants
Region of Enrollment BRAZIL	1 Participants n=39 Participants	4 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants	5 Participants n=146 Participants
Region of Enrollment CZECH REPUBLIC	4 Participants n=39 Participants	4 Participants n=41 Participants	15 Participants n=35 Participants	0 Participants n=31 Participants	23 Participants n=146 Participants
Region of Enrollment FRANCE	26 Participants n=39 Participants	21 Participants n=41 Participants	17 Participants n=35 Participants	15 Participants n=31 Participants	79 Participants n=146 Participants
Region of Enrollment GERMANY	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	19 Participants n=31 Participants	19 Participants n=146 Participants
Region of Enrollment ISRAEL	0 Participants n=39 Participants	7 Participants n=41 Participants	14 Participants n=35 Participants	0 Participants n=31 Participants	21 Participants n=146 Participants
Region of Enrollment JAPAN	0 Participants n=39 Participants	4 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants	4 Participants n=146 Participants
Region of Enrollment SPAIN	11 Participants n=39 Participants	19 Participants n=41 Participants	0 Participants n=35 Participants	25 Participants n=31 Participants	55 Participants n=146 Participants
Region of Enrollment UNITED KINGDOM	9 Participants n=39 Participants	8 Participants n=41 Participants	12 Participants n=35 Participants	0 Participants n=31 Participants	29 Participants n=146 Participants
Region of Enrollment UNITED STATES	16 Participants n=39 Participants	0 Participants n=41 Participants	7 Participants n=35 Participants	7 Participants n=31 Participants	30 Participants n=146 Participants

PRIMARY outcome

Timeframe: Up to 2 years 3 months

Population: All treated analysis set included all participants who have received at least 1 dose of study treatment. This primary outcome measure (OM) was planned to be analyzed for D-VMP, D-Rd and D-Kd cohorts only.

Outcome measures

Outcome measures
Measure	D + Bortezomib + Melphalan + Prednisone (D-VMP) n=67 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) n=65 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=66 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)	88.1 percentage of participants Interval 79.5 to 93.9	90.8 percentage of participants Interval 82.6 to 95.9	84.8 percentage of participants Interval 75.7 to 91.5	—

PRIMARY outcome

Timeframe: Up to 2 years and 3 months

VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response \[sCR\]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or \>= 90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and \<5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.

Outcome measures

Outcome measures
Measure	D + Bortezomib + Melphalan + Prednisone (D-VMP) n=67 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
D-VRd Cohort: Percentage of Participants With Very Good Partial Response (VGPR) or Better Response	71.6 percentage of participants Interval 61.2 to 80.6	—	—	—

SECONDARY outcome

Timeframe: D-VRd: Day 4 of Cycles 1 and 4 and post treatment at Week 8; D-VMP: Day 4 of Cycles 1 and 2 and post treatment at Week 8; D-Rd and D-Kd: Day 4 of Cycles 1 and 3 and post treatment at Week 8

Population: Pharmacokinetics (PK) analysis set: participants who received at least 1 dose of daratumumab SC and had at least 1 PK sample value after first dose. 'N' (number of participants analyzed): participants evaluated for this OM; 'n' (number analyzed): participants analyzed at specific timepoints. The "0" in the number analyzed field indicates that no participant was evaluable for PK at that timepoint.

Cmax was defined as maximum serum concentration observed following daratumumab administration. Each cycle for: D-VRd cohort is of 21 days, D-VMP cohort is of 42 days and D-Rd and D-Kd cohorts is of 28 days. Each cohort have a treatment period of 84 days.

Outcome measures

Outcome measures
Measure	D + Bortezomib + Melphalan + Prednisone (D-VMP) n=60 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) n=66 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=56 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=57 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
Maximum Observed Serum Concentration (Cmax) of Daratumumab Cycle 1 Day 4	100 micrograms per milliliter (mcg/mL) Standard Deviation 48.5	98.6 micrograms per milliliter (mcg/mL) Standard Deviation 51.6	108 micrograms per milliliter (mcg/mL) Standard Deviation 49.9	137 micrograms per milliliter (mcg/mL) Standard Deviation 56.7
Maximum Observed Serum Concentration (Cmax) of Daratumumab Cycle 2 Day 4	—	612 micrograms per milliliter (mcg/mL) Standard Deviation 256	—	—
Maximum Observed Serum Concentration (Cmax) of Daratumumab Cycle 3 Day 4	—	—	648 micrograms per milliliter (mcg/mL) Standard Deviation 238	869 micrograms per milliliter (mcg/mL) Standard Deviation 274
Maximum Observed Serum Concentration (Cmax) of Daratumumab Cycle 4 Day 4	746 micrograms per milliliter (mcg/mL) Standard Deviation 275	—	—	—
Maximum Observed Serum Concentration (Cmax) of Daratumumab Post-treatment Phase Week 8	263 micrograms per milliliter (mcg/mL) Standard Deviation 190	162 micrograms per milliliter (mcg/mL) Standard Deviation NA Standard deviation (SD) data is 0 as SD cannot be calculated for 1 participant.	—	49.3 micrograms per milliliter (mcg/mL) Standard Deviation 109

SECONDARY outcome

Timeframe: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months

Population: All treated analysis set included all participants who have received at least 1 dose of study treatment.

Percentage of Participants with IRRs were reported. The administration-related systemic reactions are referred to as IRRs.

Outcome measures

Outcome measures
Measure	D + Bortezomib + Melphalan + Prednisone (D-VMP) n=67 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) n=67 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=65 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=66 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
Percentage of Participants With Infusion-Related Reactions (IRRs)	9.0 percentage of participants Interval 4.0 to 16.9	9.0 percentage of participants Interval 4.0 to 16.9	4.6 percentage of participants Interval 1.3 to 11.5	4.5 percentage of participants Interval 1.3 to 11.3

SECONDARY outcome

Timeframe: From baseline up to 2 years 7 months

Population: All treated analysis set included all participants who have received at least 1 dose of study treatment. This secondary OM was planned to be analyzed for D-VMP, D-Rd and D-Kd cohorts only.

VGPR or better rate was defined as the percentage of participants who achieved VGPR or CR (including sCR) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or \>= 90% reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and \<5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.

Outcome measures

Outcome measures
Measure	D + Bortezomib + Melphalan + Prednisone (D-VMP) n=67 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) n=65 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=66 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With VGPR or Better Response	77.6 percentage of participants Interval 67.6 to 85.7	80.0 percentage of participants Interval 70.1 to 87.7	77.3 percentage of participants Interval 67.2 to 85.4	—

SECONDARY outcome

Timeframe: Up to 2 years and 3 months

Population: All treated analysis set included all participants who have received at least 1 dose of study treatment. This secondary OM was planned to be analyzed for D-VRd cohort only.

ORR was defined as the percentage of participants who achieved a PR or better, IMWG criteria, during the study or during follow up. IMWG criteria for PR \>= 50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by \>=90% or to \<200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, \>=50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>=30%, in addition to the above criteria, if present at baseline, a \>=50% reduction in the size of soft tissue plasmacytomas is also required.

Outcome measures

Outcome measures
Measure	D + Bortezomib + Melphalan + Prednisone (D-VMP) n=67 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
D-VRd Cohort: Overall Response Rate (ORR)	97.0 percentage of participants Interval 90.9 to 99.5	—	—	—

SECONDARY outcome

Timeframe: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months

Population: All treated analysis set included all participants who have received at least 1 dose of study treatment.

CR or better rate was defined as the percentage of participants with a CR or better response (that is, CR and sCR) as per IMWG criteria. CR: as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (\<) 5 percent plasma cells in bone marrow; sCR: CR plus normal FLC ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.

Outcome measures

Outcome measures
Measure	D + Bortezomib + Melphalan + Prednisone (D-VMP) n=67 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) n=67 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=65 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=66 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
Percentage of Participants With CR or Better Response	16.4 percentage of participants Interval 9.5 to 25.7	55.2 percentage of participants Interval 44.5 to 65.6	50.8 percentage of participants Interval 39.9 to 61.5	42.4 percentage of participants Interval 32.1 to 53.3

SECONDARY outcome

Timeframe: From baseline up to 2 years 7 months

Population: Analysis population included number of responders (partial response or better) in each cohort. This secondary outcome measure was planned to be analyzed for D-VMP, D-Rd and D-Kd cohorts.

DOR was defined as the time from the date of initial documented response (PR or better response) to the date of first documented evidence of progressive disease (PD) or death due to PD. 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 gram per deciliter \[g/dL\] 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	D + Bortezomib + Melphalan + Prednisone (D-VMP) n=60 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) n=61 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=56 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)	NA months Here, NA signifies that as per Kaplan-Meier estimate, the median duration of response was not estimable due to less number of events.	NA months Here, NA signifies that as per Kaplan-Meier estimate, the median duration of response was not estimable due to less number of events.	NA months Here, NA signifies that as per Kaplan-Meier estimate, the median duration of response was not estimable due to less number of events.	—

SECONDARY outcome

Timeframe: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months

Population: Immunogenicity-evaluable analysis set was defined as all participants who received at least 1 dose administration of daratumumab SC and had at least 1 immunogenicity sample for detection of anti-daratumumab antibodies after the first dose.

Percentage of participants with antibodies to daratumumab were reported.

Outcome measures

Outcome measures
Measure	D + Bortezomib + Melphalan + Prednisone (D-VMP) n=65 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) n=64 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=62 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=64 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
Percentage of Participants With Anti-Daratumumab Antibodies	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months

Population: Immunogenicity-evaluable analysis set for rHuPH20 is defined as all participants who received at least one dose of daratumumab SC and had appropriate plasma samples for detection of antibodies to rHuPH20 (at least 1 sample after the start of the first dose of daratumumab SC).

Percentage of participants with antibodies to rHuPH20 were reported.

Outcome measures

Outcome measures
Measure	D + Bortezomib + Melphalan + Prednisone (D-VMP) n=66 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) n=64 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=62 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=64 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
Percentage of Participants With Anti-rHuPH20 Antibodies	6.1 percentage of participants	3.1 percentage of participants	4.8 percentage of participants	4.7 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 years and 3 months

MRD negativity rate was defined as the percentage of participants who were considered MRD negative after MRD testing at any timepoint after the first dose by bone marrow aspirate. MRD negativity rate was assessed by next-generation sequencing at a threshold of \<10\^5.

Outcome measures

Outcome measures
Measure	D + Bortezomib + Melphalan + Prednisone (D-VMP) n=67 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.	Daratumumab + Lenalidomide + Dexamethasone (D-Rd) n=65 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) n=66 Participants Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.	Daratumumab + Carfilzomib + Dexamethasone (D-Kd) Participants received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m\^2 IV on Day 1 of Cycle 1 only, then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.
D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With Minimal Residual Disease (MRD) Negative Rate	25.4 percentage of participants Interval 16.9 to 35.6	21.5 percentage of participants Interval 13.5 to 31.6	27.3 percentage of participants Interval 18.4 to 37.7	—

Adverse Events

Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)

Serious events: 19 serious events

Other events: 67 other events

Deaths: 1 deaths

D + Bortezomib + Melphalan + Prednisone (D-VMP)

Serious events: 30 serious events

Other events: 67 other events

Deaths: 3 deaths

Daratumumab + Lenalidomide + Dexamethasone (D-Rd)

Serious events: 37 serious events

Other events: 65 other events

Deaths: 4 deaths

Daratumumab + Carfilzomib + Dexamethasone (D-Kd)

Serious events: 22 serious events

Other events: 66 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

GLOBAL MEDICAL HEAD

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 with hold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER