Trial Outcomes & Findings for A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma (NCT NCT03277105)

NCT ID: NCT03277105

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, during or after study treatment. 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)/24 hours, If the serum and urine M-proteins are not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels were required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) was 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 was also required.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 522 participants
• Primary outcome timeframe: Up to 1 year 8 months
• Results posted on: 2025-04-29

Participant Flow

Participant milestones

Measure	Daratumumab IV Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Study STARTED	259	263
Overall Study Treated (Safety Analysis Set)	258	260
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	259	263

Reasons for withdrawal

Measure	Daratumumab IV Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Study Death	129	124
Overall Study Lost to Follow-up	2	4
Overall Study Withdrawal by Subject	10	10
Overall Study Other	118	125

Baseline Characteristics

A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma

Baseline characteristics by cohort

Measure	Daratumumab IV n=259 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=263 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Total n=522 Participants Total of all reporting groups
Age, Continuous	66.8 years STANDARD_DEVIATION 10.16 • n=5 Participants	65.3 years STANDARD_DEVIATION 9.11 • n=7 Participants	66.1 years STANDARD_DEVIATION 9.66 • n=5 Participants
Sex: Female, Male Female	110 Participants n=5 Participants	127 Participants n=7 Participants	237 Participants n=5 Participants
Sex: Female, Male Male	149 Participants n=5 Participants	136 Participants n=7 Participants	285 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	227 Participants n=5 Participants	225 Participants n=7 Participants	452 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	23 Participants n=5 Participants	24 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	40 Participants n=5 Participants	32 Participants n=7 Participants	72 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) White	201 Participants n=5 Participants	207 Participants n=7 Participants	408 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	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment AUSTRALIA	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Region of Enrollment BRAZIL	10 Participants n=5 Participants	15 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment CANADA	16 Participants n=5 Participants	20 Participants n=7 Participants	36 Participants n=5 Participants
Region of Enrollment CZECH REPUBLIC	20 Participants n=5 Participants	16 Participants n=7 Participants	36 Participants n=5 Participants
Region of Enrollment FRANCE	6 Participants n=5 Participants	10 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment GREECE	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment ISRAEL	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment ITALY	10 Participants n=5 Participants	16 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment JAPAN	24 Participants n=5 Participants	18 Participants n=7 Participants	42 Participants n=5 Participants
Region of Enrollment POLAND	39 Participants n=5 Participants	26 Participants n=7 Participants	65 Participants n=5 Participants
Region of Enrollment RUSSIAN FEDERATION	28 Participants n=5 Participants	27 Participants n=7 Participants	55 Participants n=5 Participants
Region of Enrollment SOUTH KOREA	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment SPAIN	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment SWEDEN	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Region of Enrollment TAIWAN	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment UKRAINE	22 Participants n=5 Participants	25 Participants n=7 Participants	47 Participants n=5 Participants
Region of Enrollment UNITED KINGDOM	16 Participants n=5 Participants	17 Participants n=7 Participants	33 Participants n=5 Participants
Region of Enrollment UNITED STATES	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Stage of Disease (ISS) Stage I	94 Participants n=5 Participants	82 Participants n=7 Participants	176 Participants n=5 Participants
Stage of Disease (ISS) Stage II	89 Participants n=5 Participants	101 Participants n=7 Participants	190 Participants n=5 Participants
Stage of Disease (ISS) Stage III	76 Participants n=5 Participants	79 Participants n=7 Participants	155 Participants n=5 Participants
Stage of Disease (ISS) Data missing or Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Number of prior lines Less than or equal to (<=) 4 Lines	175 Participants n=5 Participants	174 Participants n=7 Participants	349 Participants n=5 Participants
Number of prior lines Greater than (>) 4 Lines	84 Participants n=5 Participants	89 Participants n=7 Participants	173 Participants n=5 Participants
Refractory status Both protease inhibitor (PI) and immunomodulatory drug (IMiD)	133 Participants n=5 Participants	125 Participants n=7 Participants	258 Participants n=5 Participants
Refractory status IMiD only	81 Participants n=5 Participants	67 Participants n=7 Participants	148 Participants n=5 Participants
Refractory status None	26 Participants n=5 Participants	41 Participants n=7 Participants	67 Participants n=5 Participants
Refractory status PI only	19 Participants n=5 Participants	30 Participants n=7 Participants	49 Participants n=5 Participants
Weight group <=65	92 Participants n=5 Participants	94 Participants n=7 Participants	186 Participants n=5 Participants
Weight group >65 - 85	105 Participants n=5 Participants	102 Participants n=7 Participants	207 Participants n=5 Participants
Weight group >85	61 Participants n=5 Participants	66 Participants n=7 Participants	127 Participants n=5 Participants
Weight group Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 1 year 8 months

Population: Intent-to-treat (ITT) population included all the randomized participants.

ORR was defined as the percentage of participants who achieved partial response (PR) or better according to International Myeloma Working Group (IMWG) criteria, during or after study treatment. 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)/24 hours, If the serum and urine M-proteins are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels were required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, >=50% reduction in bone marrow plasma cells (PCs) was 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 was also required.

Outcome measures

Measure	Daratumumab IV n=259 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=263 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Response Rate (ORR)	39.4 Percentage of participants Interval 33.4 to 45.6	43.3 Percentage of participants Interval 37.3 to 49.6

PRIMARY outcome

Timeframe: Predose on Cycle 3 Day 1 (each cycle of 28 days)

Population: Pharmacokinetics (PK) population included participants who received at least 1 administration of study drug and had at least 1 PK sample concentration value after the first dose administration. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Maximum Ctrough was defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.

Outcome measures

Measure	Daratumumab IV n=150 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=157 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Maximum Trough Concentration (Ctrough) of Daratumumab	525 micrograms per milliliter (mcg/mL) Standard Deviation 227	611 micrograms per milliliter (mcg/mL) Standard Deviation 318

SECONDARY outcome

Timeframe: Up to 3 years

Population: Safety population included all randomized participants who received at least 1 dose of study drug.

Percentage of participants with treatment-emergent infusion-related reactions were reported.

Outcome measures

Measure	Daratumumab IV n=258 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=260 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR)	34.5 Percentage of participants Interval 28.7 to 40.6	12.7 Percentage of participants Interval 8.9 to 17.4

SECONDARY outcome

Timeframe: Up to 3 years

Population: ITT population included all the randomized participants.

PFS was defined as time from date of randomization to either progression of disease (PD), death due to any cause, whichever occurs first. IMWG criteria for PD: Increase of 25% from lowest response value in any one of the following: Serum M component (absolute increase must be >=0.5 gram per deciliter (g/dL), Urine M-component (absolute increase must be >=200 mg/24 hours), Participants without measurable serum and urine Mprotein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be >10 milligrams per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC% (absolute percentage must be >=10%), definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas and development of hypercalcemia (serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

Outcome measures

Measure	Daratumumab IV n=259 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=263 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Progression Free Survival (PFS)	6.08 Months Interval 4.73 to 7.43	5.62 Months Interval 4.7 to 7.49

SECONDARY outcome

Timeframe: Up to 3 years

Population: ITT population included all the randomized participants.

VGPR or better was defined as the percentage of participants who achieved VGPR or better (VGPR, complete response (CR) or stringent complete response [sCR]), based on computerized algorithm as per 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 percent (%) reduction in serum M-protein plus urine M-protein <100 milligrams (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells (PCs) in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescencea or 2- to 4 color flow cytometry.

Outcome measures

Measure	Daratumumab IV n=259 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=263 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Percentage of Participants With Very Good Partial Response (VGPR) or Better	21.6 Percentage of participants Interval 16.8 to 27.1	23.6 Percentage of participants Interval 18.6 to 29.2

SECONDARY outcome

Timeframe: Up to 3 years

Population: ITT population included all the randomized participants.

CR or better was defined as percentage of participants with a CR or better (CR or stringent complete response [sCR]) based on computerized algorithm as per IMWG criteria. IMWG criteria for CR- negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by IHC, immunofluorescencea or 2- to 4 color flow cytometry.

Outcome measures

Measure	Daratumumab IV n=259 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=263 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Percentage of Participants With Complete Response (Including sCR) or Better	5.4 Percentage of participants Interval 3.0 to 8.9	4.6 Percentage of participants Interval 2.4 to 7.8

SECONDARY outcome

Timeframe: Up to 3 years

Population: ITT population included all the randomized participants.

Time to next therapy was defined as the time from randomization to the start of the first subsequent anti-cancer therapy.

Outcome measures

Measure	Daratumumab IV n=259 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=263 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Time to Next Therapy	9.43 Months Interval 8.15 to 10.71	8.80 Months Interval 7.59 to 10.91

SECONDARY outcome

Timeframe: Up to 3 years

Population: ITT population included all the randomized participants.

OS was defined as the time from the date of randomization to the date of the participant's death due to any cause.

Outcome measures

Measure	Daratumumab IV n=259 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=263 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Survival (OS)	25.56 Months Interval 22.05 to Lower limit of 95% CI were not estimable due to insufficient number of events.	28.19 Months Interval 22.77 to Lower limit of 95% CI were not estimable due to insufficient number of events.

SECONDARY outcome

Timeframe: Cycle 1 (Days 8,15 and 22), Cycle 2 (Days 1,8,15 and 22), Cycle 3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 and 22 (Day 1)

Population: ITT population included all the randomized participants. Here, 'N' (number of participants analysed) signifies participants who were evaluable for this outcome measure and 'n' (number of participants analyzed) signifies the number of participants analyzed at a specified time point.

Modified-CTSQ contain 9 items (2 items for Thoughts about Cancer Therapy and 7 items in a defined domain of Satisfaction with Therapy) specific to satisfaction with therapy and for comparison of SC and IV administration. Satisfaction with therapy was calculated based on 7-items using 5-point verbal rating scale, where 1= never and 5= always. Scores were averaged and transformed to a 0-100 scale; higher scores represent better health. At least 5 of the 7 items within the Satisfaction with Therapy domain had to be completed to calculate a domain score. No domain score was calculated for Thoughts about Cancer Therapy.

Outcome measures

Measure	Daratumumab IV n=239 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=263 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 9 Day 1	79.8 Units on a scale Standard Deviation 15.27	85.2 Units on a scale Standard Deviation 15.03
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 10 Day 1	79.4 Units on a scale Standard Deviation 14.73	85.8 Units on a scale Standard Deviation 13.31
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 11 Day 1	79.1 Units on a scale Standard Deviation 15.55	84.8 Units on a scale Standard Deviation 13.50
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 12 Day 1	80.3 Units on a scale Standard Deviation 15.88	85.4 Units on a scale Standard Deviation 14.70
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 13 Day 1	79.6 Units on a scale Standard Deviation 16.57	84.4 Units on a scale Standard Deviation 15.09
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 14 Day 1	80.6 Units on a scale Standard Deviation 14.62	83.5 Units on a scale Standard Deviation 15.54
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 15 Day 1	80.2 Units on a scale Standard Deviation 15.22	86.2 Units on a scale Standard Deviation 13.51
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 16 Day 1	79.4 Units on a scale Standard Deviation 14.84	88.5 Units on a scale Standard Deviation 13.10
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 17 Day 1	79.0 Units on a scale Standard Deviation 14.34	90.9 Units on a scale Standard Deviation 11.26
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 18 Day 1	84.8 Units on a scale Standard Deviation 14.13	91.4 Units on a scale Standard Deviation 11.57
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 19 Day 1	92.9 Units on a scale Standard Deviation 10.10	89.3 Units on a scale Standard Deviation 13.36
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 20 Day 1	—	86.6 Units on a scale Standard Deviation 18.53
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 21 Day 1	—	84.5 Units on a scale Standard Deviation 20.93
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 22 Day 1	—	96.4 Units on a scale
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 1 Day 8	70.5 Units on a scale Standard Deviation 15.98	76.9 Units on a scale Standard Deviation 14.64
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 1 Day 15	72.1 Units on a scale Standard Deviation 16.72	78.8 Units on a scale Standard Deviation 14.95
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 1 Day 22	72.8 Units on a scale Standard Deviation 16.20	78.7 Units on a scale Standard Deviation 15.75
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 2 Day 1	74.2 Units on a scale Standard Deviation 16.44	79.7 Units on a scale Standard Deviation 16.58
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 2 Day 8	74.8 Units on a scale Standard Deviation 15.57	80.1 Units on a scale Standard Deviation 17.24
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 2 Day 15	74.3 Units on a scale Standard Deviation 16.94	80.0 Units on a scale Standard Deviation 17.37
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 2 Day 22	75.2 Units on a scale Standard Deviation 16.47	79.3 Units on a scale Standard Deviation 18.65
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 3 Day 1	76.0 Units on a scale Standard Deviation 17.39	80.4 Units on a scale Standard Deviation 17.78
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 4 Day 1	76.6 Units on a scale Standard Deviation 17.22	79.5 Units on a scale Standard Deviation 19.88
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 5 Day 1	77.1 Units on a scale Standard Deviation 17.11	79.6 Units on a scale Standard Deviation 18.95
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 6 Day 1	76.1 Units on a scale Standard Deviation 17.79	81.9 Units on a scale Standard Deviation 18.34
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 7 Day 1	78.6 Units on a scale Standard Deviation 16.01	85.0 Units on a scale Standard Deviation 16.87
Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) Cycle 8 Day 1	79.2 Units on a scale Standard Deviation 15.54	85.0 Units on a scale Standard Deviation 15.18

SECONDARY outcome

Timeframe: Up to 3 years

Population: Participants analyzed included responders (PR or better) in ITT analysis set.

Duration of response was defined as the duration from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG criteria. PD was defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

Outcome measures

Measure	Daratumumab IV n=103 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=115 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Duration of Response	10.64 Months Interval 9.23 to 15.64	10.15 Months Interval 9.23 to 13.77

SECONDARY outcome

Timeframe: Up to 3 years

Population: Participants analyzed included responders (PR or better) in ITT analysis set.

Time to PR or better was defined as the time from randomization until onset of first response of PR or better.

Outcome measures

Measure	Daratumumab IV n=103 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=115 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Time to Partial Response (PR) or Better	1.02 Months Interval 0.9 to 24.8	1.02 Months Interval 0.9 to 9.4

SECONDARY outcome

Timeframe: Up to 3 years

Population: Participants analyzed included responders (VGPR or better) in ITT analysis set. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.

Time to VGPR or better was defined as the time from randomization until onset of first VGPR or better.

Outcome measures

Measure	Daratumumab IV n=56 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=62 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Time to Very Good Partial Response (VGPR) or Better	1.92 Months Interval 0.9 to 22.8	1.95 Months Interval 1.0 to 19.4

SECONDARY outcome

Timeframe: Up to 3 years

Population: Participants analyzed included responders (CR or better) in ITT analysis set. Here, 'N' (number of participants analysed) signifies participants who were evaluable for this outcome measure.

Time to CR or better was defined as the time from randomization until onset of first CR or better.

Outcome measures

Measure	Daratumumab IV n=14 Participants Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=12 Participants Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Time to Complete Response (CR) or Better	7.23 months Interval 1.1 to 14.9	9.26 months Interval 1.2 to 23.1

Adverse Events

Daratumumab IV

Serious events: 89 serious events

Other events: 216 other events

Deaths: 130 deaths

Daratumumab SC

Serious events: 83 serious events

Other events: 217 other events

Deaths: 126 deaths

Serious adverse events

Measure	Daratumumab IV n=258 participants at risk Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=260 participants at risk Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Blood and lymphatic system disorders Anaemia	1.6% 4/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.3% 6/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Disseminated Intravascular Coagulation	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Febrile Neutropenia	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Hyperviscosity Syndrome	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Neutropenia	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	1.6% 4/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.2% 3/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Acute Coronary Syndrome	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Angina Pectoris	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Atrial Fibrillation	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Atrioventricular Block	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Atrioventricular Block Complete	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Failure	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac Failure Chronic	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiopulmonary Failure	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Myocardial Infarction	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Myocardial Ischaemia	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Tachycardia	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Deafness Neurosensory	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Hypoacusis	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dysphagia	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.77% 2/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gingival Bleeding	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Ileus	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Inguinal Hernia	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	1.2% 3/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Oesophageal Varices Haemorrhage	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Small Intestinal Obstruction	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Subileus	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Asthenia	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.77% 2/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Chest Discomfort	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Chest Pain	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Fatigue	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders General Physical Health Deterioration	2.3% 6/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.5% 4/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Multiple Organ Dysfunction Syndrome	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Performance Status Decreased	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Pyrexia	2.3% 6/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.5% 4/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Hyperbilirubinaemia	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Acute Hepatitis B	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Bacteraemia	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Bronchiolitis	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Bronchitis	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Campylobacter Gastroenteritis	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Corona Virus Infection	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Device Related Infection	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Escherichia Infection	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Furuncle	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Hepatitis B Reactivation	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Infection	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Influenza	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.2% 3/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Listeriosis	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Lower Respiratory Tract Infection	1.6% 4/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.2% 3/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Lung Infection	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.9% 5/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Mastoiditis	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Meningitis Cryptococcal	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Meningitis Pneumococcal	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Neutropenic Sepsis	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumocystis Jirovecii Pneumonia	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	5.0% 13/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	4.6% 12/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Respiratory Syncytial Virus Bronchitis	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Respiratory Tract Infection	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.77% 2/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Rhinovirus Infection	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Sepsis	1.6% 4/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.5% 4/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Septic Shock	1.6% 4/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.2% 3/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Staphylococcal Sepsis	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Upper Respiratory Tract Infection	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Urinary Tract Infection	1.2% 3/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fall	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Femoral Neck Fracture	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Femur Fracture	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Humerus Fracture	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.77% 2/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Subdural Haematoma	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Upper Limb Fracture	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Blood Pressure Increased	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations General Physical Condition Abnormal	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Oxygen Saturation Decreased	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypercalcaemia	1.6% 4/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.77% 2/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypernatraemia	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back Pain	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.2% 3/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Bone Pain	1.2% 3/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.9% 5/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myofascial Pain Syndrome	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Neck Pain	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in Extremity	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.77% 2/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pathological Fracture	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Spinal Pain	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Trismus	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of Colon	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric Cancer	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Neoplasm Malignant	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Liver	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal Squamous Cell Carcinoma	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasmacytoma	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer Recurrent	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid Neoplasm	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour Associated Fever	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Brain Oedema	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cerebral Infarction	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cerebrovascular Accident	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Cerebrovascular Insufficiency	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Iiird Nerve Paralysis	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Monoparesis	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Peripheral Sensory Neuropathy	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Spinal Cord Compression	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Syncope	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Transient Ischaemic Attack	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Confusional State	0.78% 2/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Acute Kidney Injury	1.6% 4/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.5% 4/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Haematuria	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.77% 2/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Myeloma Cast Nephropathy	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal Failure	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.2% 3/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Pelvic Pain	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.77% 2/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Lung Disorder	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Oedema	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Thrombosis	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.77% 2/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Circulatory Collapse	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Deep Vein Thrombosis	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	0.00% 0/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.38% 1/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypotension	0.39% 1/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.

Other adverse events

Measure	Daratumumab IV n=258 participants at risk Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.	Daratumumab SC n=260 participants at risk Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Units per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Blood and lymphatic system disorders Anaemia	24.8% 64/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	27.3% 71/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Leukopenia	3.9% 10/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	6.9% 18/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Lymphopenia	6.6% 17/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	8.1% 21/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Neutropenia	13.2% 34/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	20.0% 52/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	19.4% 50/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	18.8% 49/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	8.5% 22/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	6.2% 16/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	12.4% 32/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	15.8% 41/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	12.0% 31/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	9.2% 24/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	8.1% 21/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	6.2% 16/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Asthenia	6.6% 17/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.8% 15/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Chills	12.4% 32/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.8% 15/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Fatigue	10.1% 26/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	12.7% 33/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Oedema Peripheral	5.8% 15/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.8% 10/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Pyrexia	13.2% 34/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	13.8% 36/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Bronchitis	3.5% 9/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.4% 14/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	8.1% 21/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	10.8% 28/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Upper Respiratory Tract Infection	11.6% 30/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	16.9% 44/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	6.6% 17/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.0% 13/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	7.0% 18/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	12.7% 33/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back Pain	14.0% 36/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	11.9% 31/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Bone Pain	3.9% 10/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	6.5% 17/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	6.2% 16/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	7.3% 19/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	5.0% 13/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.8% 15/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in Extremity	5.0% 13/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	7.3% 19/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	4.3% 11/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.8% 15/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Headache	9.7% 25/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.8% 15/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Insomnia	5.4% 14/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.4% 14/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	14.0% 36/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	9.6% 25/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.9% 28/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.8% 15/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	5.0% 13/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.8% 10/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	8.9% 23/258 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.	6.2% 16/260 • Up to 3 years Safety population included all randomized participants who received at least 1 dose of study drug.

Additional Information

Global Medical Head

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: ClinicalTrialDisclosure@its.jnj.com

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