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

The study population will consist of adults diagnosed with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD. The study consists of 3 phases: a screening phase (up to 28 days), a treatment phase, and a follow-up phase. Efficacy, pharmacokinetics, immunogenicity, biomarkers and safety will be assessed at scheduled time. Follow-up will continue until the end of the data collection period, approximately 24 months after the last participant was randomized or when the median overall survival for both arms has been reached, whichever occurs first. The primary hypotheses is that the ORR and maximum Ctrough for Dara SC 1800 milligram (mg) are not inferior to the ORR and maximum Ctrough, respectively, for Dara IV 16 mg per kilogram (mg/kg) in participants with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD.

Primary Outcome Measures

1. Overall Response Rate (ORR)
   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.
2. Maximum Trough Concentration (Ctrough) of Daratumumab
   Maximum Ctrough was defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.

Secondary Outcome Measures

1. Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR)
   Percentage of participants with treatment-emergent infusion-related reactions were reported.
2. Progression Free Survival (PFS)
   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.
3. Percentage of Participants With Very Good Partial Response (VGPR) or Better
   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.
4. Percentage of Participants With Complete Response (Including sCR) or Better
   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.
5. Time to Next Therapy
   Time to next therapy was defined as the time from randomization to the start of the first subsequent anti-cancer therapy.
6. Overall Survival (OS)
   OS was defined as the time from the date of randomization to the date of the participant's death due to any cause.
7. Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ)
   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.
8. Duration of Response
   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.
9. Time to Partial Response (PR) or Better
   Time to PR or better was defined as the time from randomization until onset of first response of PR or better.
10. Time to Very Good Partial Response (VGPR) or Better
    Time to VGPR or better was defined as the time from randomization until onset of first VGPR or better.
11. Time to Complete Response (CR) or Better
    Time to CR or better was defined as the time from randomization until onset of first CR or better.