Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to show that subcutaneous (SC) administration of daratumumab co-formulated with recombinant human hyaluronidase PH20 (Dara SC) is non-inferior to intravenous (IV) administration of daratumumab (Dara IV) in terms of the overall response rate (ORR) and maximum trough concentration (Ctrough).
Detailed description
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.
Interventions
DRUGDara SC
Participants will receive a fixed dose of Dara SC as 1800 mg daratumumab with rHuPH20 2000 U/mL, once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.
DRUGDara IV
Participants will receive Dara IV 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Evidence of a response (Partial response \[PR\] or better based on investigator's determination of response by international myeloma working group \[IMWG\] criteria) to at least 1 prior treatment regimen * Received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to \[\>=\] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (\>=2 cycles or 2 months of treatment) in any order during the course of treatment (except for participants who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram/day \[mg/day\] for 4 days) would not be considered prior lines of therapy * Documented multiple myeloma as defined by the criteria below: 1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria 2. Measurable disease at Screening as defined by any of the following: 1. Serum M-protein level \>=1.0 gram per deciliter (g/dL) or urine M-protein level \>=200 mg/24 hours; or 2. Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) \>=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio * Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 * Meet the clinical laboratory criteria as specified in the protocol * Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization
Exclusion criteria
* Received daratumumab or other anti-CD38 therapies previously * Received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) before treatment * Received autologous stem cell transplant within 12 weeks before the date of randomization, or the participant has previously received allogeneic stem cell transplant (regardless of timing) * Plans to undergo a stem cell transplant prior to progression of disease on this study (these participants should not be enrolled to reduce disease burden prior to transplant) * History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 1 year 8 months | 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. |
| Maximum Trough Concentration (Ctrough) of Daratumumab | Predose on Cycle 3 Day 1 (each cycle of 28 days) | Maximum Ctrough was defined as the serum predose concentration of daratumumab on Cycle 3 Day 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Very Good Partial Response (VGPR) or Better | Up to 3 years | 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. |
| Percentage of Participants With Complete Response (Including sCR) or Better | Up to 3 years | 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. |
| Time to Next Therapy | Up to 3 years | Time to next therapy was defined as the time from randomization to the start of the first subsequent anti-cancer therapy. |
| Overall Survival (OS) | Up to 3 years | OS was defined as the time from the date of randomization to the date of the participant's death due to any cause. |
| Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR) | Up to 3 years | Percentage of participants with treatment-emergent infusion-related reactions were reported. |
| Duration of Response | Up to 3 years | 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. |
| Time to Partial Response (PR) or Better | Up to 3 years | Time to PR or better was defined as the time from randomization until onset of first response of PR or better. |
| Time to Very Good Partial Response (VGPR) or Better | Up to 3 years | Time to VGPR or better was defined as the time from randomization until onset of first VGPR or better. |
| Time to Complete Response (CR) or Better | Up to 3 years | Time to CR or better was defined as the time from randomization until onset of first CR or better. |
| Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | 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) | 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. |
| Progression Free Survival (PFS) | Up to 3 years | 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. |
Countries
Australia, Brazil, Canada, Czechia, France, Greece, Israel, Italy, Japan, Poland, Russia, South Korea, Spain, Sweden, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 259 |
| 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. | 263 |
| Total | 522 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 129 | 124 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Other | 118 | 125 |
| Overall Study | Withdrawal by Subject | 10 | 10 |
Baseline characteristics
| Characteristic | Total | Daratumumab SC | Daratumumab IV |
|---|---|---|---|
| Age, Continuous | 66.1 years STANDARD_DEVIATION 9.66 | 65.3 years STANDARD_DEVIATION 9.11 | 66.8 years STANDARD_DEVIATION 10.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 14 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 452 Participants | 225 Participants | 227 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 47 Participants | 24 Participants | 23 Participants |
| Number of prior lines Greater than (>) 4 Lines | 173 Participants | 89 Participants | 84 Participants |
| Number of prior lines Less than or equal to (<=) 4 Lines | 349 Participants | 174 Participants | 175 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 72 Participants | 32 Participants | 40 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 26 Participants | 14 Participants | 12 Participants |
| Race (NIH/OMB) White | 408 Participants | 207 Participants | 201 Participants |
| Refractory status Both protease inhibitor (PI) and immunomodulatory drug (IMiD) | 258 Participants | 125 Participants | 133 Participants |
| Refractory status IMiD only | 148 Participants | 67 Participants | 81 Participants |
| Refractory status None | 67 Participants | 41 Participants | 26 Participants |
| Refractory status PI only | 49 Participants | 30 Participants | 19 Participants |
| Region of Enrollment AUSTRALIA | 28 Participants | 13 Participants | 15 Participants |
| Region of Enrollment BRAZIL | 25 Participants | 15 Participants | 10 Participants |
| Region of Enrollment CANADA | 36 Participants | 20 Participants | 16 Participants |
| Region of Enrollment CZECH REPUBLIC | 36 Participants | 16 Participants | 20 Participants |
| Region of Enrollment FRANCE | 16 Participants | 10 Participants | 6 Participants |
| Region of Enrollment GREECE | 7 Participants | 6 Participants | 1 Participants |
| Region of Enrollment ISRAEL | 13 Participants | 8 Participants | 5 Participants |
| Region of Enrollment ITALY | 26 Participants | 16 Participants | 10 Participants |
| Region of Enrollment JAPAN | 42 Participants | 18 Participants | 24 Participants |
| Region of Enrollment POLAND | 65 Participants | 26 Participants | 39 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 55 Participants | 27 Participants | 28 Participants |
| Region of Enrollment SOUTH KOREA | 11 Participants | 4 Participants | 7 Participants |
| Region of Enrollment SPAIN | 26 Participants | 12 Participants | 14 Participants |
| Region of Enrollment SWEDEN | 36 Participants | 18 Participants | 18 Participants |
| Region of Enrollment TAIWAN | 14 Participants | 8 Participants | 6 Participants |
| Region of Enrollment UKRAINE | 47 Participants | 25 Participants | 22 Participants |
| Region of Enrollment UNITED KINGDOM | 33 Participants | 17 Participants | 16 Participants |
| Region of Enrollment UNITED STATES | 6 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Female | 237 Participants | 127 Participants | 110 Participants |
| Sex: Female, Male Male | 285 Participants | 136 Participants | 149 Participants |
| Stage of Disease (ISS) Data missing or Unknown | 1 Participants | 1 Participants | 0 Participants |
| Stage of Disease (ISS) Stage I | 176 Participants | 82 Participants | 94 Participants |
| Stage of Disease (ISS) Stage II | 190 Participants | 101 Participants | 89 Participants |
| Stage of Disease (ISS) Stage III | 155 Participants | 79 Participants | 76 Participants |
| Weight group <=65 | 186 Participants | 94 Participants | 92 Participants |
| Weight group >65 - 85 | 207 Participants | 102 Participants | 105 Participants |
| Weight group >85 | 127 Participants | 66 Participants | 61 Participants |
| Weight group Not Reported | 2 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 130 / 258 | 126 / 260 |
| other Total, other adverse events | 216 / 258 | 217 / 260 |
| serious Total, serious adverse events | 89 / 258 | 83 / 260 |
Outcome results
Primary
Maximum Trough Concentration (Ctrough) of Daratumumab
Maximum Ctrough was defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daratumumab IV | Maximum Trough Concentration (Ctrough) of Daratumumab | 525 micrograms per milliliter (mcg/mL) | Standard Deviation 227 |
| Daratumumab SC | Maximum Trough Concentration (Ctrough) of Daratumumab | 611 micrograms per milliliter (mcg/mL) | Standard Deviation 318 |
Primary
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.
Time frame: Up to 1 year 8 months
Population: Intent-to-treat (ITT) population included all the randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daratumumab IV | Overall Response Rate (ORR) | 39.4 Percentage of participants |
| Daratumumab SC | Overall Response Rate (ORR) | 43.3 Percentage of participants |
Secondary
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.
Time frame: Up to 3 years
Population: Participants analyzed included responders (PR or better) in ITT analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daratumumab IV | Duration of Response | 10.64 Months |
| Daratumumab SC | Duration of Response | 10.15 Months |
Secondary
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.
Time frame: Up to 3 years
Population: ITT population included all the randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daratumumab IV | Overall Survival (OS) | 25.56 Months |
| Daratumumab SC | Overall Survival (OS) | 28.19 Months |
Secondary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 10.1 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 16.2 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab IV | 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 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 6 Day 1 | 81.9 Units on a scale | Standard Deviation 18.34 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 1 Day 15 | 78.8 Units on a scale | Standard Deviation 14.95 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 15 Day 1 | 86.2 Units on a scale | Standard Deviation 13.51 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 1 Day 22 | 78.7 Units on a scale | Standard Deviation 15.75 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 2 Day 8 | 80.1 Units on a scale | Standard Deviation 17.24 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 7 Day 1 | 85.0 Units on a scale | Standard Deviation 16.87 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 2 Day 15 | 80.0 Units on a scale | Standard Deviation 17.37 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 2 Day 1 | 79.7 Units on a scale | Standard Deviation 16.58 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 4 Day 1 | 79.5 Units on a scale | Standard Deviation 19.88 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 16 Day 1 | 88.5 Units on a scale | Standard Deviation 13.1 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 9 Day 1 | 85.2 Units on a scale | Standard Deviation 15.03 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 11 Day 1 | 84.8 Units on a scale | Standard Deviation 13.5 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 2 Day 22 | 79.3 Units on a scale | Standard Deviation 18.65 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 12 Day 1 | 85.4 Units on a scale | Standard Deviation 14.7 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 14 Day 1 | 83.5 Units on a scale | Standard Deviation 15.54 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 8 Day 1 | 85.0 Units on a scale | Standard Deviation 15.18 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 3 Day 1 | 80.4 Units on a scale | Standard Deviation 17.78 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 17 Day 1 | 90.9 Units on a scale | Standard Deviation 11.26 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 13 Day 1 | 84.4 Units on a scale | Standard Deviation 15.09 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 18 Day 1 | 91.4 Units on a scale | Standard Deviation 11.57 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 5 Day 1 | 79.6 Units on a scale | Standard Deviation 18.95 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 19 Day 1 | 89.3 Units on a scale | Standard Deviation 13.36 |
| Daratumumab SC | 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 |
| Daratumumab SC | 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 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 22 Day 1 | 96.4 Units on a scale | — |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 10 Day 1 | 85.8 Units on a scale | Standard Deviation 13.31 |
| Daratumumab SC | Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) | Cycle 1 Day 8 | 76.9 Units on a scale | Standard Deviation 14.64 |
Secondary
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.
Time frame: Up to 3 years
Population: ITT population included all the randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daratumumab IV | Percentage of Participants With Complete Response (Including sCR) or Better | 5.4 Percentage of participants |
| Daratumumab SC | Percentage of Participants With Complete Response (Including sCR) or Better | 4.6 Percentage of participants |
Secondary
Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR)
Percentage of participants with treatment-emergent infusion-related reactions were reported.
Time frame: Up to 3 years
Population: Safety population included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daratumumab IV | Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR) | 34.5 Percentage of participants |
| Daratumumab SC | Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR) | 12.7 Percentage of participants |
Secondary
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.
Time frame: Up to 3 years
Population: ITT population included all the randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daratumumab IV | Percentage of Participants With Very Good Partial Response (VGPR) or Better | 21.6 Percentage of participants |
| Daratumumab SC | Percentage of Participants With Very Good Partial Response (VGPR) or Better | 23.6 Percentage of participants |
Secondary
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.
Time frame: Up to 3 years
Population: ITT population included all the randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daratumumab IV | Progression Free Survival (PFS) | 6.08 Months |
| Daratumumab SC | Progression Free Survival (PFS) | 5.62 Months |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daratumumab IV | Time to Complete Response (CR) or Better | 7.23 months |
| Daratumumab SC | Time to Complete Response (CR) or Better | 9.26 months |
Secondary
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.
Time frame: Up to 3 years
Population: ITT population included all the randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daratumumab IV | Time to Next Therapy | 9.43 Months |
| Daratumumab SC | Time to Next Therapy | 8.80 Months |
Secondary
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.
Time frame: Up to 3 years
Population: Participants analyzed included responders (PR or better) in ITT analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daratumumab IV | Time to Partial Response (PR) or Better | 1.02 Months |
| Daratumumab SC | Time to Partial Response (PR) or Better | 1.02 Months |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daratumumab IV | Time to Very Good Partial Response (VGPR) or Better | 1.92 Months |
| Daratumumab SC | Time to Very Good Partial Response (VGPR) or Better | 1.95 Months |