Trial Outcomes & Findings for An Efficacy and Safety Study of Daratumumab in Patients With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor [PI] and Immunomodulatory Drug [IMiD]) or Are Double Refractory to a PI and an IMiD (NCT NCT01985126)

NCT ID: NCT01985126

Last Updated: 2018-06-25

Results Overview

Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5 % plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>= 90% reduction in serum M-protein plus urine M-protein level \< 100mg/24 hours; PR: \>= 50 % reduction of serum M-protein and reduction in 24 hour urinary M-protein by \>= 90% or to \<200 mg/24 hours; if the serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

124 participants

Primary outcome timeframe

Up to 14.4 Months

Results posted on

2018-06-25

Participant Flow

Participant milestones

Participant milestones
Measure	Daratumumab 8 mg/kg Daratumumab 8 milligram per kilogram (mg/kg) every 4 weeks (Q4W) until disease progression or unacceptable toxicity.	Daratumumab 16 mg/kg Daratumumab 16 mg/kg weekly for 8 weeks; then every 2 weeks (Q2W) for 16 weeks; then Q4W until disease progression or unacceptable toxicity.
Overall Study STARTED	18	106
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	18	106

Reasons for withdrawal

Reasons for withdrawal
Measure	Daratumumab 8 mg/kg Daratumumab 8 milligram per kilogram (mg/kg) every 4 weeks (Q4W) until disease progression or unacceptable toxicity.	Daratumumab 16 mg/kg Daratumumab 16 mg/kg weekly for 8 weeks; then every 2 weeks (Q2W) for 16 weeks; then Q4W until disease progression or unacceptable toxicity.
Overall Study Death	15	69
Overall Study Lost to Follow-up	0	8
Overall Study Study Terminated By Sponsor	1	22
Overall Study Withdrawal by Subject	2	7

Baseline Characteristics

An Efficacy and Safety Study of Daratumumab in Patients With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor [PI] and Immunomodulatory Drug [IMiD]) or Are Double Refractory to a PI and an IMiD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daratumumab 8 mg/kg n=18 Participants Daratumumab 8 milligram per kilogram (mg/kg) every 4 weeks (Q4W) until disease progression or unacceptable toxicity.	Daratumumab 16 mg/kg n=106 Participants Daratumumab 16 mg/kg weekly for 8 weeks; then every 2 weeks (Q2W) for 16 weeks; then Q4W until disease progression or unacceptable toxicity.	Total n=124 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	58 Participants n=7 Participants	66 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	48 Participants n=7 Participants	58 Participants n=5 Participants
Age, Continuous	64.2 years STANDARD_DEVIATION 7.72 • n=5 Participants	62.9 years STANDARD_DEVIATION 10 • n=7 Participants	63.1 years STANDARD_DEVIATION 9.68 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	54 Participants n=7 Participants	60 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	52 Participants n=7 Participants	64 Participants n=5 Participants
Region of Enrollment Canada	0 Participants n=5 Participants	22 Participants n=7 Participants	22 Participants n=5 Participants
Region of Enrollment Spain	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United States	15 Participants n=5 Participants	75 Participants n=7 Participants	90 Participants n=5 Participants
Stage of Disease (ISS) I	2 Participants n=5 Participants	26 Participants n=7 Participants	28 Participants n=5 Participants
Stage of Disease (ISS) II	8 Participants n=5 Participants	40 Participants n=7 Participants	48 Participants n=5 Participants
Stage of Disease (ISS) III	8 Participants n=5 Participants	40 Participants n=7 Participants	48 Participants n=5 Participants
Number of Prior Lines of Therapy <= 3 Lines	6 Participants n=5 Participants	19 Participants n=7 Participants	25 Participants n=5 Participants
Number of Prior Lines of Therapy > 3 Lines	12 Participants n=5 Participants	87 Participants n=7 Participants	99 Participants n=5 Participants
Refractory to Proteasome Inhibitor (PI)/ Immunomodulatory Drug (IMiD) Both a PI and IMiD	15 Participants n=5 Participants	101 Participants n=7 Participants	116 Participants n=5 Participants
Refractory to Proteasome Inhibitor (PI)/ Immunomodulatory Drug (IMiD) PI only	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Refractory to Proteasome Inhibitor (PI)/ Immunomodulatory Drug (IMiD) IMiD only	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Refractory to Proteasome Inhibitor (PI)/ Immunomodulatory Drug (IMiD) None	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 14.4 Months

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

Outcome measures

Outcome measures
Measure	Daratumumab 8 mg/kg n=18 Participants Daratumumab 8 milligram per kilogram (mg/kg) every 4 weeks (Q4W) until disease progression or unacceptable toxicity.	Daratumumab 16 mg/kg n=106 Participants Daratumumab 16 mg/kg weekly for 8 weeks; then every 2 weeks (Q2W) for 16 weeks; then Q4W until disease progression or unacceptable toxicity.
Percentage of Participants With Overall Response	11.1 percentage of participants Interval 1.4 to 34.7	29.2 percentage of participants Interval 20.8 to 38.9

SECONDARY outcome

Timeframe: Up to 14.4 Months

Population: Responders in all treated analysis set. Only those participants with confirmed PR and those who experienced progressive disease were analyzed.

Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in IMWG criteria. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component (the absolute increase must be \>=0.5 g/dL) and/or; urine M-component (the absolute increase must be \>=200 mg/24 hours) and/or; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase must be \>10 milligram per deciliter (mg/dL); Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL or 2.65 millimole per liter \[mmol/L\]) that can be attributed solely to the plasma cell proliferative disorder.

Outcome measures

Outcome measures
Measure	Daratumumab 8 mg/kg n=2 Participants Daratumumab 8 milligram per kilogram (mg/kg) every 4 weeks (Q4W) until disease progression or unacceptable toxicity.	Daratumumab 16 mg/kg n=31 Participants Daratumumab 16 mg/kg weekly for 8 weeks; then every 2 weeks (Q2W) for 16 weeks; then Q4W until disease progression or unacceptable toxicity.
Duration of Response	NA months Interval 1.8 to These were Kaplan-Meier estimates. Median and/or upper limit of CI was not estimable because a small proportion of responders either progressed or died due to progressive disease.	7.4 months Interval 5.5 to These were Kaplan-Meier estimates. Median and/or upper limit of CI was not estimable because a small proportion of responders either progressed or died due to progressive disease.

SECONDARY outcome

Timeframe: Approximately up to 3 years

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

Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Daratumumab 8 mg/kg n=18 Participants Daratumumab 8 milligram per kilogram (mg/kg) every 4 weeks (Q4W) until disease progression or unacceptable toxicity.	Daratumumab 16 mg/kg n=106 Participants Daratumumab 16 mg/kg weekly for 8 weeks; then every 2 weeks (Q2W) for 16 weeks; then Q4W until disease progression or unacceptable toxicity.
Overall Survival	19.45 months Interval 7.72 to 26.81	18.60 months Interval 13.67 to 25.0

SECONDARY outcome

Timeframe: Up to 14.4 Months

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

Clinical benefit rate defined as percentage of participants who achieved minimal response (MR) or better. MR: \>=25% but \<= 49% reduction of serum M-protein and reduction in urine M-protein by 50%-89%. If present at baseline 25% to 49% reduction in size of soft tissue plasmacytomas.

Outcome measures

Outcome measures
Measure	Daratumumab 8 mg/kg n=18 Participants Daratumumab 8 milligram per kilogram (mg/kg) every 4 weeks (Q4W) until disease progression or unacceptable toxicity.	Daratumumab 16 mg/kg n=106 Participants Daratumumab 16 mg/kg weekly for 8 weeks; then every 2 weeks (Q2W) for 16 weeks; then Q4W until disease progression or unacceptable toxicity.
Percentage of Participants With Clinical Benefit	22.2 percentage of participants Interval 6.4 to 47.6	34.0 percentage of participants Interval 25.0 to 43.8

SECONDARY outcome

Timeframe: Up to 14.4 Months

Population: Responders in all treated analysis set. Only those participants with confirmed PR were analyzed.

Time to response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better).

Outcome measures

Outcome measures
Measure	Daratumumab 8 mg/kg n=2 Participants Daratumumab 8 milligram per kilogram (mg/kg) every 4 weeks (Q4W) until disease progression or unacceptable toxicity.	Daratumumab 16 mg/kg n=31 Participants Daratumumab 16 mg/kg weekly for 8 weeks; then every 2 weeks (Q2W) for 16 weeks; then Q4W until disease progression or unacceptable toxicity.
Time to Response	0.99 months Interval 0.95 to 1.02	0.99 months Interval 0.9 to 5.6

SECONDARY outcome

Timeframe: Up to 14.4 Months

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

Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first.

Outcome measures

Outcome measures
Measure	Daratumumab 8 mg/kg n=18 Participants Daratumumab 8 milligram per kilogram (mg/kg) every 4 weeks (Q4W) until disease progression or unacceptable toxicity.	Daratumumab 16 mg/kg n=106 Participants Daratumumab 16 mg/kg weekly for 8 weeks; then every 2 weeks (Q2W) for 16 weeks; then Q4W until disease progression or unacceptable toxicity.
Progression Free Survival	4.86 months Interval 1.84 to Upper limit of CI was not estimable due to the relatively short duration of follow-up.	3.65 months Interval 2.76 to 4.63

SECONDARY outcome

Timeframe: Up to 14.4 Months

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

Time to progression was defined as the number of days from the date of first dose of daratumumab to the date of first record of disease progression.

Outcome measures

Outcome measures
Measure	Daratumumab 8 mg/kg n=18 Participants Daratumumab 8 milligram per kilogram (mg/kg) every 4 weeks (Q4W) until disease progression or unacceptable toxicity.	Daratumumab 16 mg/kg n=106 Participants Daratumumab 16 mg/kg weekly for 8 weeks; then every 2 weeks (Q2W) for 16 weeks; then Q4W until disease progression or unacceptable toxicity.
Time to Disease Progression	4.86 months Interval 1.84 to Upper limit of CI was not estimable due to the relatively short duration of follow-up.	3.71 months Interval 2.79 to 5.39

Adverse Events

Daratumumab 8 mg/kg

Serious events: 6 serious events

Other events: 18 other events

Deaths: 0 deaths

Daratumumab 16 mg/kg

Serious events: 33 serious events

Other events: 105 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Director Clinical Leader

Janssen Research & Development, LLC

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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 in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Daratumumab 8 mg/kg n=18 participants at risk Daratumumab 8 milligram per kilogram (mg/kg) every 4 weeks (Q4W) until disease progression or unacceptable toxicity.	Daratumumab 16 mg/kg n=106 participants at risk Daratumumab 16 mg/kg weekly for 8 weeks; then every 2 weeks (Q2W) for 16 weeks; then Q4W until disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anaemia	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	1.9% 2/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Cardiac disorders Cardiac Failure Congestive	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Cardiac disorders Cardio-Respiratory Arrest	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Gastrointestinal disorders Abdominal Pain	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Gastrointestinal disorders Faecal Incontinence	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Gastrointestinal disorders Large Intestinal Obstruction	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Gastrointestinal disorders Nausea	5.6% 1/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.00% 0/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Gastrointestinal disorders Pancreatitis	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Gastrointestinal disorders Vomiting	5.6% 1/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.00% 0/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
General disorders Asthenia	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
General disorders Fatigue	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
General disorders General Physical Health Deterioration	5.6% 1/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	4.7% 5/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
General disorders Pyrexia	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Hepatobiliary disorders Hepatic Failure	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations Bronchitis	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations H1n1 Influenza	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations Herpes Zoster	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations Lobar Pneumonia	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	1.9% 2/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations Parainfluenzae Virus Infection	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations Pneumonia	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	3.8% 4/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations Pneumonia Streptococcal	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations Pyelonephritis	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations Respiratory Tract Infection	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations Sepsis	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations Soft Tissue Infection	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Infections and infestations Varicella	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Injury, poisoning and procedural complications Spinal Compression Fracture	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Injury, poisoning and procedural complications Subdural Haematoma	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Investigations Blood Creatinine Increased	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Investigations Oxygen Saturation Abnormal	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	3.8% 4/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Metabolism and nutrition disorders Hyperuricaemia	5.6% 1/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.00% 0/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Musculoskeletal and connective tissue disorders Back Pain	5.6% 1/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	1.9% 2/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Musculoskeletal and connective tissue disorders Pathological Fracture	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Musculoskeletal and connective tissue disorders Spinal Column Stenosis	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Musculoskeletal and connective tissue disorders Spinal Pain	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma Cell Leukaemia	5.6% 1/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.00% 0/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Nervous system disorders Headache	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Nervous system disorders Spinal Cord Compression	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Nervous system disorders Syncope	5.6% 1/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.00% 0/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Nervous system disorders Tremor	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Psychiatric disorders Delirium	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Renal and urinary disorders Acute Kidney Injury	5.6% 1/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.00% 0/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Renal and urinary disorders Haematuria	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Renal and urinary disorders Renal Impairment	5.6% 1/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.00% 0/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Renal and urinary disorders Urinary Retention	5.6% 1/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.00% 0/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Renal and urinary disorders Urinary Tract Obstruction	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Reproductive system and breast disorders Pelvic Pain	5.6% 1/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.00% 0/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Respiratory, thoracic and mediastinal disorders Acute Pulmonary Oedema	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	5.6% 1/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Respiratory, thoracic and mediastinal disorders Pneumonia Aspiration	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Vascular disorders Deep Vein Thrombosis	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.
Vascular disorders Hypotension	0.00% 0/18 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.	0.94% 1/106 • Approximately up to 3.8 years All treated Analysis Set included all participants who received at least 1 dose of daratumumab.