Trial Outcomes & Findings for Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma. (NCT NCT03158688)

Last Updated: 2025-05-09

Results Overview

Progression-free survival (PFS) was defined as the time from randomization to the earlier of disease progression or death due to any cause. Participants were evaluated for disease response and progression according to the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) as assessed by an Independent Review Committee (IRC). The duration of PFS was right censored for participants who met any of the following conditions: 1. no baseline/post-baseline disease assessments; 2. started a new anti myeloma therapy before documentation of progressive disease or death; 3. progressive disease or death immediately after more than 70 days without disease assessment visit or; 4. alive without documentation of disease progression before the analysis trigger date (PA DCO); 5. lost to follow-up or withdrawn consent.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

466 participants

Primary outcome timeframe

From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Results posted on

2025-05-09

Participant Flow

This study was conducted at 102 centers. 569 participants were screened and 466 were enrolled. Primary analysis (PA) data cutoff (DCO): 14-Jul-2019. Final analysis (FA) DCO: 15-Apr-2022.

Participants were randomized in 1:2 ratio to arms KD vs KdD after being stratified by 1) International Staging System (ISS) stage (Stage 1-2 vs Stage 3) at screening, 2) prior proteasome inhibitor exposure (yes/no), 3) number of prior lines of therapy (1 vs ≥ 2), and 4) prior cluster differentiation antigen 38 (CD38) antibody therapy (yes/no).

Participant milestones

Participant milestones
Measure	Kd - Carfilzomib and Dexamethasone Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Study STARTED	154	312
Overall Study Treated	153	308
Overall Study COMPLETED	49	102
Overall Study NOT COMPLETED	105	210

Reasons for withdrawal

Reasons for withdrawal
Measure	Kd - Carfilzomib and Dexamethasone Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Study Withdrawal by Subject	14	28
Overall Study Decision by sponsor	13	37
Overall Study Lost to Follow-up	4	3
Overall Study Death	74	142

Baseline Characteristics

Data was not available for some participants.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Kd - Carfilzomib and Dexamethasone n=154 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=312 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.	Total n=466 Participants Total of all reporting groups
Age, Continuous	64.3 years STANDARD_DEVIATION 9.6 • n=154 Participants	62.9 years STANDARD_DEVIATION 10.0 • n=312 Participants	63.4 years STANDARD_DEVIATION 9.9 • n=466 Participants
Age, Customized 18 - 64 years	77 Participants n=154 Participants	163 Participants n=312 Participants	240 Participants n=466 Participants
Age, Customized 65 - 74 years	55 Participants n=154 Participants	121 Participants n=312 Participants	176 Participants n=466 Participants
Age, Customized 75 - 84 years	22 Participants n=154 Participants	28 Participants n=312 Participants	50 Participants n=466 Participants
Age, Customized >=85 years	0 Participants n=154 Participants	0 Participants n=312 Participants	0 Participants n=466 Participants
Sex: Female, Male Female	63 Participants n=154 Participants	135 Participants n=312 Participants	198 Participants n=466 Participants
Sex: Female, Male Male	91 Participants n=154 Participants	177 Participants n=312 Participants	268 Participants n=466 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=154 Participants	7 Participants n=312 Participants	8 Participants n=466 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	146 Participants n=154 Participants	291 Participants n=312 Participants	437 Participants n=466 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=154 Participants	14 Participants n=312 Participants	21 Participants n=466 Participants
Race/Ethnicity, Customized Asian	20 Participants n=154 Participants	46 Participants n=312 Participants	66 Participants n=466 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=154 Participants	7 Participants n=312 Participants	9 Participants n=466 Participants
Race/Ethnicity, Customized White	123 Participants n=154 Participants	243 Participants n=312 Participants	366 Participants n=466 Participants
Race/Ethnicity, Customized Other	9 Participants n=154 Participants	16 Participants n=312 Participants	25 Participants n=466 Participants
Frailty Status as Assessed by Investigator Fit	68 Participants n=154 Participants	176 Participants n=312 Participants	244 Participants n=466 Participants
Frailty Status as Assessed by Investigator Intermediate fitness	36 Participants n=154 Participants	54 Participants n=312 Participants	90 Participants n=466 Participants
Frailty Status as Assessed by Investigator Frail	9 Participants n=154 Participants	10 Participants n=312 Participants	19 Participants n=466 Participants
Frailty Status as Assessed by Investigator Not available	37 Participants n=154 Participants	66 Participants n=312 Participants	103 Participants n=466 Participants
Frailty Status as Assessed by Investigator Missing	4 Participants n=154 Participants	6 Participants n=312 Participants	10 Participants n=466 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Disease status 0 or 1	147 Participants n=154 Participants	295 Participants n=312 Participants	442 Participants n=466 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Disease status 2	7 Participants n=154 Participants	15 Participants n=312 Participants	22 Participants n=466 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Missing	0 Participants n=154 Participants	2 Participants n=312 Participants	2 Participants n=466 Participants
Time from Initial Diagnosis to Randomization	44.03 months STANDARD_DEVIATION 36.57 • n=149 Participants • Data was not available for some participants.	47.86 months STANDARD_DEVIATION 34.69 • n=297 Participants • Data was not available for some participants.	46.58 months STANDARD_DEVIATION 35.34 • n=446 Participants • Data was not available for some participants.
Risk Group as Determined by Fluorescent in situ Hybridization (FISH) High risk	26 Participants n=154 Participants	48 Participants n=312 Participants	74 Participants n=466 Participants
Risk Group as Determined by Fluorescent in situ Hybridization (FISH) Standard risk	56 Participants n=154 Participants	108 Participants n=312 Participants	164 Participants n=466 Participants
Risk Group as Determined by Fluorescent in situ Hybridization (FISH) Unknown	72 Participants n=154 Participants	156 Participants n=312 Participants	228 Participants n=466 Participants
Stratification Factor: International Staging System (ISS) Stage per IxRS Stage I or II	127 Participants n=154 Participants	252 Participants n=312 Participants	379 Participants n=466 Participants
Stratification Factor: International Staging System (ISS) Stage per IxRS Stage III	27 Participants n=154 Participants	60 Participants n=312 Participants	87 Participants n=466 Participants
Stratification Factor: Lines of Prior Treatment per IxRS 1 prior treatment	67 Participants n=154 Participants	133 Participants n=312 Participants	200 Participants n=466 Participants
Stratification Factor: Lines of Prior Treatment per IxRS > = 2 prior treatments	87 Participants n=154 Participants	179 Participants n=312 Participants	266 Participants n=466 Participants
Stratification Factor: Prior Proteasome Inhibitor Treatment per IxRS Yes	139 Participants n=154 Participants	279 Participants n=312 Participants	418 Participants n=466 Participants
Stratification Factor: Prior Proteasome Inhibitor Treatment per IxRS No	15 Participants n=154 Participants	33 Participants n=312 Participants	48 Participants n=466 Participants
Stratification Factor: Prior CD38 Antibody Therapy per IxRS Yes	0 Participants n=154 Participants	1 Participants n=312 Participants	1 Participants n=466 Participants
Stratification Factor: Prior CD38 Antibody Therapy per IxRS No	154 Participants n=154 Participants	311 Participants n=312 Participants	465 Participants n=466 Participants
Geographic Regions North America	12 Participants n=154 Participants	21 Participants n=312 Participants	33 Participants n=466 Participants
Geographic Regions Europe	103 Participants n=154 Participants	207 Participants n=312 Participants	310 Participants n=466 Participants
Geographic Regions Asia Pacific	39 Participants n=154 Participants	84 Participants n=312 Participants	123 Participants n=466 Participants

PRIMARY outcome

Timeframe: From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Population: Intent to Treat Population

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=154 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=312 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Progression-free Survival (PFS) as Assessed by the Independent Review Committee (PA DCO Only) Participants with PFS events	68 Participants	110 Participants
Progression-free Survival (PFS) as Assessed by the Independent Review Committee (PA DCO Only) Participants who were censored	86 Participants	202 Participants

SECONDARY outcome

Timeframe: From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Population: Intent to Treat Population

Overall response rate was defined as the percentage of participants in each treatment group who achieve partial response (PR) or better per the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) as their best response. Complete Response (CR): No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-component with urine M-component \<100 mg/24 hours. Partial Response (PR): ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to \< 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline. 95% CIs for proportions were estimated using the Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=154 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=312 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Response (OR) as Assessed by the Independent Review Committee (PA DCO Only)	74.7 percentage of participants Interval 67.0 to 81.3	84.3 percentage of participants Interval 79.8 to 88.1

SECONDARY outcome

Timeframe: 12 Months (8- to 13-month window)

Population: Intent to Treat Population

MRD\[-\]CR at 12 months was defined as achievement of CR per IMWG-URC by IRC and MRD\[-\] status as assessed by next-generation sequencing (NGS; at a 10\^-5 level) at the 12 months landmark (8 to 13 month window).

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=154 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=312 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Minimal Residual Disease Negative Complete Response Rate (MRD[-]CR) at 12 Months as Assessed by the Independent Review Committee	1.9 percentage of participants Interval 0.4 to 5.6	12.8 percentage of participants Interval 9.3 to 17.0

SECONDARY outcome

Timeframe: Up to 58 months after the first participant was enrolled (at FA DCO, a median of 40.29 weeks of treatment [any study drug] in the Kd group and 79.29 weeks of treatment [any study drug] in the KdD group; FA DCO was 15 Apr 2022)

Population: Intent to Treat Population

Overall survival was defined as the time from randomization until death from any cause. Deaths collected via public source, after end of study were included. Medians were estimated using the Kaplan-Meier method. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. Participants still alive were censored at the date last known to be alive.

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=154 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=312 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Survival	43.6 months Interval 35.3 to Not enough events to estimate the upper 95% CI	50.8 months Interval 44.7 to Not enough events to estimate the upper 95% CI

SECONDARY outcome

Timeframe: PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks

Population: Safety Population

Treatment-emergent adverse events are defined as any adverse event with an onset after the administration of the first dose of any study treatment and within the end of study or 30 days of the last dose of any study treatment, whichever occurs earlier. The severity of adverse events was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal. Treatment-related adverse events are treatment-emergent adverse events considered related to at least one study drug by the investigator, including those with unknown relationship.

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=153 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=308 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: Related and serious TEAEs	32 Participants	84 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: Related TEAEs: discon of carfilzomib	21 Participants	50 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: Related TEAEs: discon of daratumumab	NA Participants not relevant for this treatment arm	15 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: Related TEAEs: discon of dexamethasone	24 Participants	19 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: Related Fatal TEAEs	0 Participants	5 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: All TEAEs	149 Participants	306 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: All TEAEs	147 Participants	306 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: TEAEs: Severity Grade >=3	113 Participants	253 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: TEAEs: Serious Adverse Events	70 Participants	173 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: TEAEs: Leading to discon of carfilzomib	33 Participants	65 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: TEAEs: Leading to discon of daratumumab	NA Participants not relevant for this treatment arm	28 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: TEAEs: Leading to discon of dexamethasone	37 Participants	33 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: Fatal TEAEs	8 Participants	30 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: Treatment-related TEAEs	129 Participants	260 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: Related TEAEs: Grade >=3	74 Participants	187 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: Related and serious TEAEs	34 Participants	102 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: Related TEAEs: discon of carfilzomib	22 Participants	69 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: TEAEs: Severity Grade >=3	120 Participants	273 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: TEAEs: Serious Adverse Events	80 Participants	211 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: TEAEs: Leading to discontinuation of carfilzomib	37 Participants	98 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: TEAEs: Leading to discontinuation of daratumumab	NA Participants not relevant for this treatment arm	43 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: TEAEs: Leading to discon of dexamethasone	40 Participants	58 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: Related TEAEs: discon of daratumumab	NA Participants not relevant for this treatment arm	18 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: Related TEAEs: discon of dexamethasone	24 Participants	30 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: Related Fatal TEAEs	0 Participants	5 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: Fatal TEAEs	11 Participants	39 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: Treatment-related TEAEs	131 Participants	267 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) FA DCO: Related TEAEs: Grade >=3	82 Participants	206 Participants

SECONDARY outcome

Timeframe: From Day 1 until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Population: Participants who responded in the Intent to Treat Population

Duration of response (DOR) was defined as the time (in months) from first evidence of partial response (PR) or better per IMWG-URC by IRC to the earlier of disease progression or death due to any cause for participants with a best response of PR or better. For those who are alive and have not experienced disease progression at the time of data cutoff for analysis, duration of response was right-censored. Medians were estimated using the Kaplan-Meier method. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=115 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=263 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Kaplan-Meier Estimate for Duration of Response (DOR) (PA DCO Only)	16.6 months Interval 13.9 to Not enough events to estimate the upper 95% CI	NA months Not enough events to estimate a median and confidence intervals

SECONDARY outcome

Timeframe: PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks

Population: Intent to Treat Population

Time to next treatment was defined as the time (in months) from randomization to the initiation of subsequent non-protocol anti-cancer treatment for multiple myeloma. Time to next treatment for participants who do not start the subsequent treatment for multiple myeloma was censored at the date when the participant's information was last available. Medians of TTNT duration were estimated using the Kaplan-Meier method. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=154 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=312 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Kaplan-Meier Estimate for Time to Next Treatment (TTNT) PA DCO	17.3 months Interval 13.5 to Not enough events to estimate the upper 95% CI	NA months Not enough events to estimate a median and confidence intervals
Kaplan-Meier Estimate for Time to Next Treatment (TTNT) FA DCO	17.8 months Interval 13.5 to 23.1	37.4 months Interval 30.1 to 47.8

SECONDARY outcome

Timeframe: From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Population: Intent to Treat Population

Time to progression was defined as the time (in months) from randomization to documented disease progression. Participants who did not have documented disease progression were censored at the date when data was last available.

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=154 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=312 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Kaplan-Meier Estimates for Time to Progression (TTP) as Assessed by the Independent Review Committee (PA DCO Only)	17.5 months Interval 13.2 to Not enough events to estimate the upper 95% CI	NA months Not enough events to estimate a median and confidence intervals

SECONDARY outcome

Timeframe: Randomization to Months 3, 6, 12, and 18

Population: Intent to Treat Population

Time to progression was defined as the time (in months) from randomization to documented disease progression. This outcome reports TTP as the percentage of participants who were event free (that is, they had not had disease progression) at the specified time frames. Independent Review Committee assessment for this outcome measure was not planned after the primary analysis. 95% CIs for event-free rates were estimated using the method by Kalbfleisch and Prentice (1980) with log-log transformation.

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=154 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=312 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Time to Progression (TTP): Percentage of Participants Who Had Not Had Disease Progression as Assessed by the Independent Review Committee at Months 3, 6, 12, and 18 (PA DCO Only) 3 months	90.0 percentage of participants Interval 83.7 to 93.9	95.3 percentage of participants Interval 92.1 to 97.2
Time to Progression (TTP): Percentage of Participants Who Had Not Had Disease Progression as Assessed by the Independent Review Committee at Months 3, 6, 12, and 18 (PA DCO Only) 6 months	79.4 percentage of participants Interval 71.6 to 85.3	86.4 percentage of participants Interval 81.8 to 89.9
Time to Progression (TTP): Percentage of Participants Who Had Not Had Disease Progression as Assessed by the Independent Review Committee at Months 3, 6, 12, and 18 (PA DCO Only) 12 months	62.7 percentage of participants Interval 53.6 to 70.5	77.5 percentage of participants Interval 72.1 to 82.0
Time to Progression (TTP): Percentage of Participants Who Had Not Had Disease Progression as Assessed by the Independent Review Committee at Months 3, 6, 12, and 18 (PA DCO Only) 18 months	45.1 percentage of participants Interval 34.5 to 55.4	68.5 percentage of participants Interval 62.2 to 74.0

SECONDARY outcome

Timeframe: From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Population: Participants who responded in the Intent to Treat Population

Time to overall response was defined as the time from randomization to the earliest date a response of partial response (PR) or better as per IMWG-URC is first achieved and subsequently confirmed for participants with a best response of PR or better.

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=115 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=263 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Time to Overall Response as Assessed by the Independent Review Committee (PA DCO Only)	1.5 months Standard Deviation 1.1	1.4 months Standard Deviation 1.4

SECONDARY outcome

Timeframe: PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks

Population: Intent to Treat Population

A measure of the persistence of the CR (includes strict CR) per International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) and MRD\[-\] status as assessed by next-generation sequencing (NGS; at a 10\^-5 level) for 12 months or more after achieving MRD\[-\]CR status. 95% confidence intervals (CIs) for proportions were estimated using the Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=154 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=312 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Percentage of Participants Who Achieved and Maintained a Minimal Residual Disease Negative Complete Response (MRD[-]CR) for 12 Months or More PA DCO	0.0 percentage of participants Interval 0.0 to 2.4	0.0 percentage of participants Interval 0.0 to 1.2
Percentage of Participants Who Achieved and Maintained a Minimal Residual Disease Negative Complete Response (MRD[-]CR) for 12 Months or More FA DCO	0.0 percentage of participants Interval 0.0 to 2.4	5.8 percentage of participants Interval 3.5 to 9.0

SECONDARY outcome

Timeframe: From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Population: Intent to Treat Population

The percentage of participants in each treatment group who achieved stringent complete response (sCR) or CR per IMWG-URC, as assessed by the IRC, as their best response is presented.

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=154 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=312 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Percentage of Participants With a Complete Response (CR) as Assessed by the Independent Review Committee (PA DCO Only)	10.4 percentage of participants Interval 6.1 to 16.3	28.5 percentage of participants Interval 23.6 to 33.9

SECONDARY outcome

Timeframe: 12 Months (8- to 13-month window)

Population: Intent to Treat Population

MRD\[-\] at 12-month was defined as achievement of MRD\[-\] status as assessed by next-generation sequencing (NGS; at a 10\^-5 level) at the 12 months landmark (from 8 months to 13 months window). 95% confidence intervals (CIs) for proportions were estimated using the Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=154 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=312 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Percentage of Participants Who Achieved Minimal Residual Disease Negative (MRD[-]) Status as Assessed by Next Generation Sequencing at 12 Months	5.2 percentage of participants Interval 2.3 to 10.0	18.3 percentage of participants Interval 14.1 to 23.0

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) up to 236.3 weeks (longest treatment duration as of the FA DCO)

Population: Intent to Treat Population

Health-related quality of life was assessed with the use of the European Organization for Research and Treatment of Cancer Quality of Life Core Module (QLQ-C30) questionnaire, a validated instrument in multiple myeloma patients. Scores range from 0 to 100, with higher scores indicating better health related quality of life. QLQ-C30 questionnaire was administered prior to dosing every 28 ± 7 days starting from cycle 1 day 1 through first follow-up visit (30 days \[+3\] after last dose of all study drugs).

Outcome measures

Outcome measures
Measure	Kd - Carfilzomib and Dexamethasone n=154 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	KdD - Carfilzomib, Dexamethasone and Daratumumab n=312 Participants Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 50	61.11 score on a scale Standard Deviation 9.62	68.75 score on a scale Standard Deviation 13.09
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 41	66.07 score on a scale Standard Deviation 13.26	68.46 score on a scale Standard Deviation 19.37
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 42	63.69 score on a scale Standard Deviation 15.19	67.16 score on a scale Standard Deviation 18.77
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 43	67.22 score on a scale Standard Deviation 15.89	63.30 score on a scale Standard Deviation 19.91
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 44	61.81 score on a scale Standard Deviation 15.27	65.50 score on a scale Standard Deviation 18.21
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 14	67.66 score on a scale Standard Deviation 17.03	66.12 score on a scale Standard Deviation 16.60
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 13	67.49 score on a scale Standard Deviation 16.51	67.00 score on a scale Standard Deviation 18.21
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 16	68.21 score on a scale Standard Deviation 16.44	66.41 score on a scale Standard Deviation 18.69
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 17	69.44 score on a scale Standard Deviation 14.92	69.81 score on a scale Standard Deviation 15.28
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 18	66.67 score on a scale Standard Deviation 16.50	66.29 score on a scale Standard Deviation 16.38
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 19	69.68 score on a scale Standard Deviation 17.50	68.00 score on a scale Standard Deviation 17.33
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 20	71.04 score on a scale Standard Deviation 14.49	66.43 score on a scale Standard Deviation 19.52
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 15	69.34 score on a scale Standard Deviation 15.31	67.61 score on a scale Standard Deviation 17.68
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 31	68.06 score on a scale Standard Deviation 16.24	67.33 score on a scale Standard Deviation 18.81
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 32	66.67 score on a scale Standard Deviation 19.62	67.91 score on a scale Standard Deviation 18.45
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 21	70.94 score on a scale Standard Deviation 15.87	67.42 score on a scale Standard Deviation 16.25
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 22	68.52 score on a scale Standard Deviation 12.30	67.51 score on a scale Standard Deviation 17.90
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 23	69.52 score on a scale Standard Deviation 16.41	66.67 score on a scale Standard Deviation 17.63
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 24	68.10 score on a scale Standard Deviation 18.24	68.00 score on a scale Standard Deviation 16.51
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 25	67.93 score on a scale Standard Deviation 16.15	66.21 score on a scale Standard Deviation 16.78
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 26	70.71 score on a scale Standard Deviation 18.65	66.12 score on a scale Standard Deviation 17.54
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 27	65.23 score on a scale Standard Deviation 14.78	66.52 score on a scale Standard Deviation 18.35
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 28	63.22 score on a scale Standard Deviation 19.61	67.28 score on a scale Standard Deviation 18.66
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 29	66.67 score on a scale Standard Deviation 19.25	67.22 score on a scale Standard Deviation 18.10
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 30	67.01 score on a scale Standard Deviation 17.63	67.23 score on a scale Standard Deviation 18.52
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 40	58.33 score on a scale Standard Deviation 14.25	67.74 score on a scale Standard Deviation 19.34
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 33	67.75 score on a scale Standard Deviation 15.35	67.95 score on a scale Standard Deviation 18.92
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 34	68.18 score on a scale Standard Deviation 15.78	69.86 score on a scale Standard Deviation 17.77
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 35	65.91 score on a scale Standard Deviation 15.62	69.51 score on a scale Standard Deviation 18.00
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 36	63.77 score on a scale Standard Deviation 18.22	68.22 score on a scale Standard Deviation 16.93
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 37	67.50 score on a scale Standard Deviation 18.91	68.63 score on a scale Standard Deviation 19.01
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 48	61.11 score on a scale Standard Deviation 9.62	68.56 score on a scale Standard Deviation 13.35
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 38	65.20 score on a scale Standard Deviation 18.69	69.25 score on a scale Standard Deviation 18.47
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 39	64.71 score on a scale Standard Deviation 15.46	68.38 score on a scale Standard Deviation 19.15
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 45	67.59 score on a scale Standard Deviation 12.11	66.87 score on a scale Standard Deviation 15.53
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 46	64.58 score on a scale Standard Deviation 13.91	67.89 score on a scale Standard Deviation 17.66
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 49	61.11 score on a scale Standard Deviation 9.62	68.42 score on a scale Standard Deviation 13.49
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 47	66.67 score on a scale Standard Deviation 0.00	68.52 score on a scale Standard Deviation 13.74
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 51	63.89 score on a scale Standard Deviation 4.81	67.36 score on a scale Standard Deviation 11.49
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 3	66.13 score on a scale Standard Deviation 18.12	63.10 score on a scale Standard Deviation 18.24
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 52	54.17 score on a scale Standard Deviation 17.68	62.04 score on a scale Standard Deviation 17.24
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Baseline	66.19 score on a scale Standard Deviation 19.19	61.79 score on a scale Standard Deviation 20.37
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 2	64.35 score on a scale Standard Deviation 16.25	61.00 score on a scale Standard Deviation 19.65
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 4	66.67 score on a scale Standard Deviation 15.01	63.47 score on a scale Standard Deviation 18.66
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 5	67.62 score on a scale Standard Deviation 17.19	64.45 score on a scale Standard Deviation 16.76
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 6	68.06 score on a scale Standard Deviation 15.80	65.92 score on a scale Standard Deviation 16.85
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 7	69.33 score on a scale Standard Deviation 14.68	65.73 score on a scale Standard Deviation 16.59
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 8	69.44 score on a scale Standard Deviation 17.82	66.34 score on a scale Standard Deviation 16.64
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 9	65.72 score on a scale Standard Deviation 15.90	67.82 score on a scale Standard Deviation 15.53
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 10	68.38 score on a scale Standard Deviation 14.56	67.98 score on a scale Standard Deviation 16.26
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 11	67.42 score on a scale Standard Deviation 15.24	68.52 score on a scale Standard Deviation 17.37
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 53	—	61.11 score on a scale Standard Deviation 9.62
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Follow-up	61.00 score on a scale Standard Deviation 23.04	59.90 score on a scale Standard Deviation 18.02
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Cycle 12	65.13 score on a scale Standard Deviation 14.94	67.47 score on a scale Standard Deviation 17.16

Adverse Events

Kd - Carfilzomib and Dexamethasone

Serious events: 80 serious events

Other events: 137 other events

Deaths: 80 deaths

KdD - Carfilzomib, Dexamethasone and Daratumumab

Serious events: 211 serious events

Other events: 295 other events

Deaths: 148 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER