Trial Outcomes & Findings for Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma (NCT NCT02136134)

Last Updated: 2025-08-29

Results Overview

PFS was defined as duration from date of randomization to either progressive disease (PD)/death, whichever occurred first. PD was defined as meeting any one of following criteria: Increase of greater than equal to (\>=)25 percent (%) in level of serum M-protein from lowest response value and absolute increase must be \>=0.5 gram per deciliter (g/dL); Increase of \>=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be \>=200 mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of \>=25% in difference between involved and uninvolved FLC levels from lowest response value and absolute increase must be \>10 mg/dL; Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

498 participants

Primary outcome timeframe

From the date of randomization to either progressive disease or death, whichever occurred first (approximately 1 year 4 months)

Results posted on

2025-08-29

Participant Flow

Participant milestones

Participant milestones
Measure	Bortezomib + Dexamethasone (Vd) Participants received bortezomib 1.3 milligrams per square meter (mg/m\^2) subcutaneous (SC) injection on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 milligrams (mg) orally (PO) on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles. Participants who met sponsor confirmed disease progression eligibility criteria received daratumumab monotherapy as a subsequent antimyeloma therapy as follow: daratumumab 16 milligrams per kilogram (mg/kg) intravenous (IV) infusion or daratumumab SC injection (1800 mg fixed dose) weekly for the first 2 cycles, every 2 weeks from Cycle 3 to 6, and then every 4 weeks thereafter.	Daratumumab + Bortezomib and Dexamethasone (DVd) Participants received daratumumab 16 mg/kg IV infusion weekly or daratumumab SC injection (1800 mg fixed dose) for the first 3 cycles, on Day 1 of Cycles 4-8, and then every 4 weeks thereafter, bortezomib 1.3 mg/m\^2 SC injection administration on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles.
Overall Study STARTED	247	251
Overall Study Daratumumab Monotherapy	87	0
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	247	251

Reasons for withdrawal

Reasons for withdrawal
Measure	Bortezomib + Dexamethasone (Vd) Participants received bortezomib 1.3 milligrams per square meter (mg/m\^2) subcutaneous (SC) injection on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 milligrams (mg) orally (PO) on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles. Participants who met sponsor confirmed disease progression eligibility criteria received daratumumab monotherapy as a subsequent antimyeloma therapy as follow: daratumumab 16 milligrams per kilogram (mg/kg) intravenous (IV) infusion or daratumumab SC injection (1800 mg fixed dose) weekly for the first 2 cycles, every 2 weeks from Cycle 3 to 6, and then every 4 weeks thereafter.	Daratumumab + Bortezomib and Dexamethasone (DVd) Participants received daratumumab 16 mg/kg IV infusion weekly or daratumumab SC injection (1800 mg fixed dose) for the first 3 cycles, on Day 1 of Cycles 4-8, and then every 4 weeks thereafter, bortezomib 1.3 mg/m\^2 SC injection administration on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles.
Overall Study Death	170	148
Overall Study Withdrawal by Subject	19	10
Overall Study Lost to Follow-up	3	3
Overall Study Uspecified	55	90

Baseline Characteristics

Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bortezomib + Dexamethasone (Vd) n=247 Participants Participants received bortezomib 1.3 milligrams per square meter (mg/m\^2) subcutaneous (SC) injection on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 milligrams (mg) orally (PO) on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles. Participants who met sponsor confirmed disease progression eligibility criteria received daratumumab monotherapy as a subsequent antimyeloma therapy as follow: daratumumab 16 milligrams per kilogram (mg/kg) intravenous (IV) infusion or daratumumab SC injection (1800 mg fixed dose) weekly for the first 2 cycles, every 2 weeks from Cycle 3 to 6, and then every 4 weeks thereafter.	Daratumumab + Bortezomib and Dexamethasone (DVd) n=251 Participants Participants received daratumumab 16 mg/kg IV infusion weekly or daratumumab SC injection (1800 mg fixed dose) for the first 3 cycles, on Day 1 of Cycles 4-8, and then every 4 weeks thereafter, bortezomib 1.3 mg/m\^2 SC injection administration on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles.	Total n=498 Participants Total of all reporting groups
Age, Continuous	63.9 years STANDARD_DEVIATION 9.81 • n=5 Participants	62.8 years STANDARD_DEVIATION 9.66 • n=7 Participants	63.4 years STANDARD_DEVIATION 9.74 • n=5 Participants
Sex: Female, Male Female	99 Participants n=5 Participants	114 Participants n=7 Participants	213 Participants n=5 Participants
Sex: Female, Male Male	148 Participants n=5 Participants	137 Participants n=7 Participants	285 Participants n=5 Participants
Region of Enrollment Australia	20 participants n=5 Participants	23 participants n=7 Participants	43 participants n=5 Participants
Region of Enrollment Brazil	9 participants n=5 Participants	13 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Czech Republic	19 participants n=5 Participants	16 participants n=7 Participants	35 participants n=5 Participants
Region of Enrollment Germany	21 participants n=5 Participants	21 participants n=7 Participants	42 participants n=5 Participants
Region of Enrollment Hungary	14 participants n=5 Participants	16 participants n=7 Participants	30 participants n=5 Participants
Region of Enrollment Italy	25 participants n=5 Participants	24 participants n=7 Participants	49 participants n=5 Participants
Region of Enrollment Korea, Republic of	8 participants n=5 Participants	10 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Mexico	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Netherlands	14 participants n=5 Participants	11 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Poland	18 participants n=5 Participants	16 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Russian Federation	13 participants n=5 Participants	21 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Spain	19 participants n=5 Participants	10 participants n=7 Participants	29 participants n=5 Participants
Region of Enrollment Sweden	9 participants n=5 Participants	10 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment Turkey	14 participants n=5 Participants	14 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Ukraine	22 participants n=5 Participants	28 participants n=7 Participants	50 participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	16 participants n=7 Participants	37 participants n=5 Participants
Stage of Disease (ISS) I	96 participants n=5 Participants	98 participants n=7 Participants	194 participants n=5 Participants
Stage of Disease (ISS) II	100 participants n=5 Participants	94 participants n=7 Participants	194 participants n=5 Participants
Stage of Disease (ISS) III	51 participants n=5 Participants	59 participants n=7 Participants	110 participants n=5 Participants
No. of Prior Lines of Therapy 1	113 participants n=5 Participants	122 participants n=7 Participants	235 participants n=5 Participants
No. of Prior Lines of Therapy 2	74 participants n=5 Participants	70 participants n=7 Participants	144 participants n=5 Participants
No. of Prior Lines of Therapy 3	32 participants n=5 Participants	37 participants n=7 Participants	69 participants n=5 Participants
No. of Prior Lines of Therapy >3	28 participants n=5 Participants	22 participants n=7 Participants	50 participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization to either progressive disease or death, whichever occurred first (approximately 1 year 4 months)

Population: The intent-to-treat (ITT) population included all randomized participants.

Outcome measures

Outcome measures
Measure	Bortezomib + Dexamethasone (Vd) n=247 Participants Participants received bortezomib 1.3 milligrams per square meter (mg/m\^2) subcutaneous (SC) injection on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 milligrams (mg) orally (PO) on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles. Participants who met sponsor-confirmed disease progression eligibility criteria received daratumumab monotherapy as a subsequent antimyeloma therapy as follow: daratumumab 16 milligrams per kilogram (mg/kg) intravenous (IV) infusion or daratumumab SC injection (1800 mg fixed dose) weekly for the first 2 cycles, every 2 weeks from Cycle 3 to 6, and then every 4 weeks thereafter.	Daratumumab + Bortezomib and Dexamethasone (DVd) n=251 Participants Participants received daratumumab 16 mg/kg IV infusion weekly or daratumumab SC injection (1800 mg fixed dose) for the first 3 cycles, on Day 1 of Cycles 4-8, and then every 4 weeks thereafter, bortezomib 1.3 mg/m\^2 SC injection administration on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles.
Progression-free Survival (PFS)	7.16 months Interval 6.21 to 7.85	NA months Interval 12.25 to Median and Upper limit of 95% CI was not estimable due to short follow-up by participants.

SECONDARY outcome

Timeframe: From the date of randomization to the date of first documented evidence of progression or death due to PD whichever occurred first (approximately 6 years 9 months)

Population: The intent-to-treat (ITT) population included all randomized participants.

TTP was defined as time from date of randomization to date of first documented evidence of progressive disease (PD). PD was defined as meeting any one of following criteria: Increase of \>=25% in level of serum M-protein from lowest response value and absolute increase must be \>=0.5 g/dL; Increase of \>=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be \>=200 mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of \>=25% in difference between involved and uninvolved free light chain (FLC) levels from lowest response value and absolute increase must be \>10 milligram per deciliter (mg/dL); Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to Plasma Cell (PC) proliferative disorder.

Outcome measures

Outcome measures
Measure	Bortezomib + Dexamethasone (Vd) n=247 Participants Participants received bortezomib 1.3 milligrams per square meter (mg/m\^2) subcutaneous (SC) injection on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 milligrams (mg) orally (PO) on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles. Participants who met sponsor-confirmed disease progression eligibility criteria received daratumumab monotherapy as a subsequent antimyeloma therapy as follow: daratumumab 16 milligrams per kilogram (mg/kg) intravenous (IV) infusion or daratumumab SC injection (1800 mg fixed dose) weekly for the first 2 cycles, every 2 weeks from Cycle 3 to 6, and then every 4 weeks thereafter.	Daratumumab + Bortezomib and Dexamethasone (DVd) n=251 Participants Participants received daratumumab 16 mg/kg IV infusion weekly or daratumumab SC injection (1800 mg fixed dose) for the first 3 cycles, on Day 1 of Cycles 4-8, and then every 4 weeks thereafter, bortezomib 1.3 mg/m\^2 SC injection administration on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles.
Time to Disease Progression (TTP)	7.29 months Interval 6.41 to 8.08	NA months Interval 12.25 to Median and Upper limit of 95% CI was not estimable due to short follow-up by participants.

SECONDARY outcome

Timeframe: Up to disease progression (approximately 6 years 9 months)

Population: The response evaluable analysis set is defined as participants who have a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 administration of study treatment, and had at least 1 post baseline disease assessment.

Response rate of VGPR or better was defined as the percentage of participants who achieved VGPR and CR (including sCR) according to the IMWG criteria during or after the study treatment. IMWG criteria for 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, if the serum and urine M-protein are not measurable, a decrease of \>90% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, in addition to the above criteria, if present at baseline, a \>=50% reduction in the size of soft tissue plasmacytomas is also required; CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and \<5% PCs in bone marrow; sCR: CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry.

Outcome measures

Outcome measures
Measure	Bortezomib + Dexamethasone (Vd) n=234 Participants Participants received bortezomib 1.3 milligrams per square meter (mg/m\^2) subcutaneous (SC) injection on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 milligrams (mg) orally (PO) on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles. Participants who met sponsor-confirmed disease progression eligibility criteria received daratumumab monotherapy as a subsequent antimyeloma therapy as follow: daratumumab 16 milligrams per kilogram (mg/kg) intravenous (IV) infusion or daratumumab SC injection (1800 mg fixed dose) weekly for the first 2 cycles, every 2 weeks from Cycle 3 to 6, and then every 4 weeks thereafter.	Daratumumab + Bortezomib and Dexamethasone (DVd) n=240 Participants Participants received daratumumab 16 mg/kg IV infusion weekly or daratumumab SC injection (1800 mg fixed dose) for the first 3 cycles, on Day 1 of Cycles 4-8, and then every 4 weeks thereafter, bortezomib 1.3 mg/m\^2 SC injection administration on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles.
Percentage of Participants With a Very Good Partial Response (VGPR) or Better	29.1 percentage of participants Interval 23.3 to 35.3	59.2 percentage of participants Interval 52.7 to 65.4

SECONDARY outcome

Timeframe: Up to disease progression (approximately 6 years 9 months)

Population: The response-evaluable analysis set is defined as participants who have confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 administration of study treatment and had at least 1 post baseline disease assessment.

The Overall response rate was defined as the percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to the International Myeloma Working Group (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, 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	Bortezomib + Dexamethasone (Vd) n=234 Participants Participants received bortezomib 1.3 milligrams per square meter (mg/m\^2) subcutaneous (SC) injection on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 milligrams (mg) orally (PO) on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles. Participants who met sponsor-confirmed disease progression eligibility criteria received daratumumab monotherapy as a subsequent antimyeloma therapy as follow: daratumumab 16 milligrams per kilogram (mg/kg) intravenous (IV) infusion or daratumumab SC injection (1800 mg fixed dose) weekly for the first 2 cycles, every 2 weeks from Cycle 3 to 6, and then every 4 weeks thereafter.	Daratumumab + Bortezomib and Dexamethasone (DVd) n=240 Participants Participants received daratumumab 16 mg/kg IV infusion weekly or daratumumab SC injection (1800 mg fixed dose) for the first 3 cycles, on Day 1 of Cycles 4-8, and then every 4 weeks thereafter, bortezomib 1.3 mg/m\^2 SC injection administration on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles.
Overall Response Rate (ORR)	63.2 percentage of participants Interval 56.7 to 69.4	82.9 percentage of participants Interval 77.5 to 87.5

SECONDARY outcome

Timeframe: Up to disease progression (approximately 6 years 9 months)

Population: The intent-to-treat (ITT) population included all randomized participants.

The Minimal Residual Disease negativity rate was defined as the percentage of participants who had negative MRD assessment at any timepoint after the first dose of study drugs by evaluation of bone marrow aspirates or whole blood. MRD was assessed in participants who achieved complete response or stringent complete response (CR/sCR). IMWG criteria for CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and \<5% PCs in bone marrow; sCR: CR plus normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry.

Outcome measures

Outcome measures
Measure	Bortezomib + Dexamethasone (Vd) n=247 Participants Participants received bortezomib 1.3 milligrams per square meter (mg/m\^2) subcutaneous (SC) injection on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 milligrams (mg) orally (PO) on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles. Participants who met sponsor-confirmed disease progression eligibility criteria received daratumumab monotherapy as a subsequent antimyeloma therapy as follow: daratumumab 16 milligrams per kilogram (mg/kg) intravenous (IV) infusion or daratumumab SC injection (1800 mg fixed dose) weekly for the first 2 cycles, every 2 weeks from Cycle 3 to 6, and then every 4 weeks thereafter.	Daratumumab + Bortezomib and Dexamethasone (DVd) n=251 Participants Participants received daratumumab 16 mg/kg IV infusion weekly or daratumumab SC injection (1800 mg fixed dose) for the first 3 cycles, on Day 1 of Cycles 4-8, and then every 4 weeks thereafter, bortezomib 1.3 mg/m\^2 SC injection administration on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles.
Percentage of Participants With Negative Minimal Residual Disease (MRD)	2.8 percentage of participants	13.5 percentage of participants

SECONDARY outcome

Timeframe: Up to 6 years 9 months

Population: The intent-to-treat (ITT) population included all randomized participants.

Overall Survival was measured from the date of randomization to the date of the participant's death.

Outcome measures

Outcome measures
Measure	Bortezomib + Dexamethasone (Vd) n=247 Participants Participants received bortezomib 1.3 milligrams per square meter (mg/m\^2) subcutaneous (SC) injection on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 milligrams (mg) orally (PO) on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles. Participants who met sponsor-confirmed disease progression eligibility criteria received daratumumab monotherapy as a subsequent antimyeloma therapy as follow: daratumumab 16 milligrams per kilogram (mg/kg) intravenous (IV) infusion or daratumumab SC injection (1800 mg fixed dose) weekly for the first 2 cycles, every 2 weeks from Cycle 3 to 6, and then every 4 weeks thereafter.	Daratumumab + Bortezomib and Dexamethasone (DVd) n=251 Participants Participants received daratumumab 16 mg/kg IV infusion weekly or daratumumab SC injection (1800 mg fixed dose) for the first 3 cycles, on Day 1 of Cycles 4-8, and then every 4 weeks thereafter, bortezomib 1.3 mg/m\^2 SC injection administration on Days 1, 4, 8, and 11 of each 21-day cycle (8 treatment cycles) and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles.
Overall Survival (OS)	38.51 months Interval 31.18 to 46.23	49.58 months Interval 42.18 to 62.32

Adverse Events

Bortezomib + Dexamethasone (Vd)

Serious events: 81 serious events

Other events: 217 other events

Deaths: 0 deaths

Daratumumab + Bortezomib and Dexamethasone (DVd)

Serious events: 134 serious events

Other events: 238 other events

Deaths: 0 deaths

Switch From Bortezomib + Dexamethasone (Vd) to Daratumumab Monotherapy

Serious events: 7 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Director, Clinical Research

Janssen R&D US

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