Trial Outcomes & Findings for A Study to Evaluate Dara-CyBorD in Previously Untreated and Relapsed Subjects With Multiple Myeloma (NCT NCT02951819)

Last Updated: 2021-10-08

Results Overview

Percentage of participants who achieved CR or VGPR (as per International Myeloma Working Group \[IMWG\] criteria) was reported. CR: negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (\<) 5 percent (%) plasma cells (PC) in bone marrow. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (\>=) 90% reduction in serum M-protein plus urine M-protein level \< 100 milligram per 24 hours (mg/24hours).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

101 participants

Primary outcome timeframe

After 4 cycles of Induction (Approximately 4 months)

Results posted on

2021-10-08

Participant Flow

Participant milestones

Participant milestones
Measure	Newly Diagnosed Multiple Myeloma (NDMM) Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT): Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Overall Study STARTED	87	14
Overall Study Treated	86	14
Overall Study COMPLETED	59	7
Overall Study NOT COMPLETED	28	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Newly Diagnosed Multiple Myeloma (NDMM) Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT): Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Overall Study Death	9	7
Overall Study Withdrawal by Subject	3	0
Overall Study Adverse Event	1	0
Overall Study Lack of Efficacy	4	0
Overall Study Lost to Follow-up	1	0
Overall Study Progressive Disease	1	0
Overall Study Other	9	0

Baseline Characteristics

A Study to Evaluate Dara-CyBorD in Previously Untreated and Relapsed Subjects With Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Newly Diagnosed Multiple Myeloma (NDMM) n=86 Participants Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT): Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) n=14 Participants Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Total n=100 Participants Total of all reporting groups
Age, Continuous	63.6 years STANDARD_DEVIATION 9 • n=5 Participants	66.4 years STANDARD_DEVIATION 8.97 • n=7 Participants	64 years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	4 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	10 Participants n=7 Participants	64 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	79 Participants n=5 Participants	12 Participants n=7 Participants	91 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) White	67 Participants n=5 Participants	14 Participants n=7 Participants	81 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment UNITED STATES	86 Participants n=5 Participants	14 Participants n=7 Participants	100 Participants n=5 Participants

PRIMARY outcome

Timeframe: After 4 cycles of Induction (Approximately 4 months)

Population: Response-evaluable set includes all enrolled participants who had measurable disease, received at least 1 dose of study treatment, and had at least 1 efficacy evaluation assessment.

Outcome measures

Outcome measures
Measure	Newly Diagnosed Multiple Myeloma (NDMM) n=86 Participants Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) n=14 Participants Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Percentage of Participants Who Achieved Complete Response (CR) or Very Good Partial Response (VGPR)	44.2 Percentage of Participants Interval 33.5 to 55.3	57.1 Percentage of Participants Interval 28.9 to 82.3

SECONDARY outcome

Timeframe: After 4 Cycles of Induction (4 months), at End of Induction (4 to 8 months) and at the End of Maintenance (12 months)

Population: Response-evaluable set includes all enrolled participants who had measurable disease, received at least 1 dose of study treatment, and had at least 1 efficacy evaluation assessment.

ORR: percentage of participants achieved PR or better (PR,VGPR,CR,sCR) per IMWG. CR:negative immunofixation on serum, urine, disappearance of soft tissue plasmacytomas,\<5% PCs in bone marrow(BM). sCR:CR plus normal FLC ratio,absence of clonal cells in BM by immunohistochemistry, immunofluorescence. VGPR:Serum, urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24hours. PR:\>=50% reduction of serum M-protein and reduction in 24hours urinary M-protein by \>=90% or to \<200mg/24hours. If serum, urine M-protein unmeasurable, a\>=50% decrease in difference involved and uninvolved FLC levels required in place of M-protein criteria. If serum, urine M-protein not measurable, serum free light assay is not measurable,\>=50% reduction in PCs required in place of M-protein,provided baseline bone marrow PCs% \>=30%, if present at baseline, a \>=50% reduction in size of soft tissue plasmacytomas is also required.

Outcome measures

Outcome measures
Measure	Newly Diagnosed Multiple Myeloma (NDMM) n=86 Participants Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) n=14 Participants Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Overall Response Rate (ORR) At the End of Induction	87.2 Percentage of participants Interval 78.3 to 93.4	78.6 Percentage of participants Interval 49.2 to 95.3
Overall Response Rate (ORR) After 4 Cycles of Induction	79.1 Percentage of participants Interval 69.0 to 87.1	71.4 Percentage of participants Interval 41.9 to 91.6
Overall Response Rate (ORR) At the End of Maintenance	89.5 Percentage of participants Interval 81.1 to 95.1	85.7 Percentage of participants Interval 57.2 to 98.2

SECONDARY outcome

Timeframe: Up to 36 months

Population: Response-evaluable set includes all enrolled participants who had measurable disease, received at least 1 dose of study treatment, and had at least 1 efficacy evaluation assessment.

Time to VGPR or Better response was defined as duration from the date of first dose (start of induction) to the date of initial documentation of the response (VGPR or better) which was confirmed by a repeated measurement as required by the IMWG criteria. VGPR is defined by IMWG criteria as serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (\>=) 90 % reduction in serum M-protein plus urine M-protein level \< 100 milligram/24 hours (mg/24 hours).

Outcome measures

Outcome measures
Measure	Newly Diagnosed Multiple Myeloma (NDMM) n=86 Participants Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) n=14 Participants Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Time to Very Good Partial Response (VGPR) or Better	3.8 Months Interval 2.8 to 4.9	1.8 Months Interval 1.0 to 4.7

SECONDARY outcome

Timeframe: Up to 12 months

Population: Response-evaluable set includes all enrolled participants who had measurable disease, received at least 1 dose of study treatment, and had at least 1 efficacy evaluation assessment.

Time to PR or Better response was defined as duration from the date of first dose (start of induction) to the date of initial documentation of the response (PR or better) which was confirmed by a repeated measurement as required by the IMWG criteria. PR is defined as per IMWG criteria as \>= 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>= 90% or to \< 200 mg/24hours. If the serum and urine M-protein are unmeasurable, a\>= 50% decrease in the difference between involved and uninvolved Free light chain (FLC) levels is required in the 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 plasma cells is required in place of M-protein, provided baseline bone marrow plasma cells percentage was \>=30%. In addition to the above listed criteria, if present at baseline, a \>= 50% reduction in the size of soft tissue plasmacytomas is also required.

Outcome measures

Outcome measures
Measure	Newly Diagnosed Multiple Myeloma (NDMM) n=86 Participants Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) n=14 Participants Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Time to Partial Response (PR) or Better	1.0 Months Interval 1.0 to 1.0	1.0 Months Interval 0.9 to 7.4

SECONDARY outcome

Timeframe: Up to 36 months

Population: Population included responders (PR or better) in response-evaluable set.

DOR was defined for participants with a confirmed response (PR or better) 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 or death due to progressive disease. PR:\>=50% reduction of serum M-protein and reduction in 24hours urinary M-protein by \>=90% or to \<200 mg/24hours. If serum and urine M-protein are unmeasurable, a \>=50% decrease in difference involved and uninvolved FLC levels required in place of M-protein criteria. If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, \>=50% reduction in PCs is required in place of M-protein, provided baseline bone marrow PCs % 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	Newly Diagnosed Multiple Myeloma (NDMM) n=77 Participants Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) n=12 Participants Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Duration of Response (DOR)	NA Months NA indicates that the median, lower and upper limit of confidence interval (CI) was not estimable due to insufficient number of events to determine this value.	20.7 Months Interval 5.9 to NA indicates that the upper limit of CI was not estimable due to insufficient number of events to determine this value.

SECONDARY outcome

Timeframe: Up to 36 months

Population: Full analysis set is defined as enrolled participants who provided informed consent and met eligibility criteria.

PFS: duration from date of first dose (start of induction) to date of first documented evidence of progressive disease (PD) based on computerized algorithm per IMWG criteria or death due to any cause, whichever occurred first. PD: 25% increase from lowest response value in one of following: Serum and urine M-component (absolute increase \>=0.5 g/dL and \>=200 mg/24 hours respectively);Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase\>10 mg/dL);Only participants without measurable serum and urine M-protein levels, without measurable disease by FLC levels, bone marrow PC% (absolute % \>=10%); Bone marrow PC%: absolute% \>10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/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	Newly Diagnosed Multiple Myeloma (NDMM) n=87 Participants Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) n=14 Participants Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Progression Free Survival (PFS)	NA Months NA indicates that the median, lower and upper limit of CI was not estimable due to insufficient number of events to determine this value.	21.7 Months Interval 6.8 to NA indicates that the upper limit of CI was not estimable due to insufficient number of events to determine this value.

SECONDARY outcome

Timeframe: Approximately 15 months

Population: Full Analysis Set defined as enrolled subjects who provided informed consent and met eligibility criteria.

TTP was defined as the time between the date of first dose (start of induction) and the date of first documented evidence of confirmed PD, as defined in the IMWG response criteria. PD per IMWG criteria: Increase of 25% from lowest response value in one of following: Serum and urine M-component (absolute increase \>=0.5 g/deciliter (dL) and \>=200 mg/24 hours respectively); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase\>10 mg/dL); Only participants without measurable serum and urine M-protein levels, without measurable disease by FLC levels, bone marrow PC% (absolute % \>=10%); Bone marrow PC%: absolute% \>10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to the PC proliferative disorder.

Outcome measures

Outcome measures
Measure	Newly Diagnosed Multiple Myeloma (NDMM) n=87 Participants Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) n=14 Participants Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Time to Disease Progression (TTP)	NA Months NA indicates that the median, lower and upper limit of CI was not estimable due to insufficient number of events to determine this value.	13.31 Months Interval 6.8 to 13.31

SECONDARY outcome

Timeframe: Up to 36 months

Population: Full analysis set is defined as enrolled participants who provided informed consent and met eligibility criteria.

Overall survival (OS) was measured from the date of first dose (start of induction) to the date of death due to any cause.

Outcome measures

Outcome measures
Measure	Newly Diagnosed Multiple Myeloma (NDMM) n=87 Participants Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) n=14 Participants Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Overall Survival (OS)	NA Months NA indicates that median, lower and upper limit of CI was not estimable due to insufficient number of events to determine this value.	NA Months Interval 11.3 to NA indicates that median and upper limit of CI was not estimable due to insufficient number of events to determine this value.

SECONDARY outcome

Timeframe: Up to 36 months

Population: Safety Analysis Set defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between administration of study drug and approximately up to 36 months that were absent before treatment or that worsened relative to pre-treatment state.

Outcome measures

Outcome measures
Measure	Newly Diagnosed Multiple Myeloma (NDMM) n=86 Participants Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) n=14 Participants Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Percentage of Participants With Treatment Emergent-Adverse Event	100.0 Percentage of participants	100.0 Percentage of participants

Adverse Events

Newly Diagnosed Multiple Myeloma (NDMM)

Serious events: 28 serious events

Other events: 86 other events

Deaths: 9 deaths

Relapsed Multiple Myeloma (RMM)

Serious events: 5 serious events

Other events: 14 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Director

Janssen Scientific Affairs

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

Measure	Newly Diagnosed Multiple Myeloma (NDMM) n=86 participants at risk Induction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). Consolidation therapy (CT): Participants who were considered eligible for transplant underwent autologous stem cell transplantation \[ASCT\] at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).	Relapsed Multiple Myeloma (RMM) n=14 participants at risk Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m\^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m\^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 (\[if with CyBorD\] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Blood and lymphatic system disorders Febrile Neutropenia	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Cardiac disorders Atrial Fibrillation	4.7% 4/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Cardiac disorders Atrial Flutter	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Gastrointestinal disorders Haemorrhoidal Haemorrhage	0.00% 0/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	7.1% 1/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Gastrointestinal disorders Vomiting	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
General disorders Fatigue	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
General disorders Non-Cardiac Chest Pain	2.3% 2/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
General disorders Pyrexia	2.3% 2/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Hepatobiliary disorders Cholecystitis Acute	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Bacteraemia	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Bacterial Sepsis	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Bronchitis	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Cellulitis	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Diverticulitis	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Herpes Zoster Disseminated	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Influenza	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Otitis Externa	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Pneumonia	2.3% 2/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	14.3% 2/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Pneumonia Parainfluenzae Viral	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Pneumonia Streptococcal	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Urinary Tract Infection	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Infections and infestations Viral Upper Respiratory Tract Infection	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Injury, poisoning and procedural complications Femur Fracture	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Injury, poisoning and procedural complications Hip Fracture	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Injury, poisoning and procedural complications Pelvic Fracture	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Injury, poisoning and procedural complications Toxicity to Various Agents	0.00% 0/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	7.1% 1/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Metabolism and nutrition disorders Dehydration	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Metabolism and nutrition disorders Hyperglycaemia	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Metabolism and nutrition disorders Hyponatraemia	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Musculoskeletal and connective tissue disorders Back Pain	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Musculoskeletal and connective tissue disorders Bone Lesion	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute Leukaemia	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Nervous system disorders Syncope	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Psychiatric disorders Mental Status Changes	2.3% 2/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Renal and urinary disorders Nephrotic Syndrome	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	7.1% 1/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Respiratory, thoracic and mediastinal disorders Laryngeal Oedema	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	2.3% 2/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	7.1% 1/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Vascular disorders Deep Vein Thrombosis	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Vascular disorders Hypotension	1.2% 1/86 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).	0.00% 0/14 • Up to 36 months Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).