- KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone, or with lenalidomide plus dexamethasone, or with daratumumab plus dexamethasone, ... Read More Close
DKd:
KYPROLIS® + daratumumab + dexamethasone
A proven combination at first relapse
Phase 3, randomized, open-label, multicenter trial that compared KYPROLIS® plus daratumumab and dexamethasone (DKd) to KYPROLIS® plus dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma who had received 1 to 3 prior lines of therapy. 466 patients were randomized 2:1 to receive DKd (n = 312) or Kd (n = 154) with KYPROLIS® 56 mg/m² twice weekly for 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was PFS. Select secondary endpoints included ORR, MRD-negative CR rate at 12 months, and safety.1,2
DKd reduced the risk of progression or death by 41% vs Kd1
At a median follow-up of nearly 28 months (HR = 0.59; 95% CI: 0.45-0.78).
Primary results were reported after a median follow-up of ~ 17 months.
Median PFS was not reached for DKd vs 15.8 months for Kd (HR = 0.63; 95%
CI:
0.46-0.85; P = 0.0014, one-sided).1,2
CI, confidence interval; CR, complete response; DKd, carfilzomib + daratumumab + dexamethasone; HR, hazard ratio; Kd, carfilzomib + dexamethasone; mPFS, median progression-free survival; MRD, minimal residual disease; ORR, overall response rate; PFS, progression-free survival.
DKd delivered deep responses with high MRD-negativity rates*
DKd MRD negativity at
12-month landmark
DKd MRD negativity at any time
from final follow-up analysis
(median follow up of 4.2 years)
*MRD negativity rates were higher in the DKd arm than in the Kd arm of the study. MRD-negative CR (at the 10-5 level) is defined as achievement of CR per the IMWG-URC and MRD-negative status assessed by the next-generation sequencing assay (ClonoSEQ) at the 12-month landmark (from 8-month to 13-month window).2
CR, complete response; DKd, carfilzomib + daratumumab + dexamethasone; Kd, carfilzomib + dexamethasone; MRD, minimal residual disease; ORR, overall response rate; PR, partial response; RRMM, relapsed or refractory multiple myeloma; VGPR, very good partial response.
These results represent prespecified subgroup analyses of the CANDOR study; however, these analyses were not study objectives and the study was therefore not powered or adjusted for multiplicity to assess efficacy in these subgroups.3
*Data from primary analysis with a median follow-up of ~ 17 months.
†High-risk defined as a patient with cytogenetic abnormalities [t(4;14), t(4;16), or deletion 17p] that are considered high-risk.3
‡Standard-risk defined as a patient without cytogenetic abnormalities [t(4;14), t(4;16), or deletion 17p] that are considered high-risk.3
CI, confidence interval; DKd, carfilzomib + daratumumab + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group Performance Status; ISS, International Staging System; Kd, carfilzomib + dexamethasone; Len, lenalidomide; PFS, progression-free survival; PI, proteasome inhibitor.
Study Design
DKd vs Kd (CANDOR)
Inclusion and exclusion criteria5
Key eligibility criteria (N = 466):
Key exclusion criteria:
*Carfilzomib at 56 mg/m2 administered twice weekly; 20 mg/m2 administered on Days 1 and 2 of Cycle 1 only.
†The first dose of daratumumab is split over Days 1 and 2 of Cycle 1 (8 mg/kg each day).
‡For patients > 75 years of age, 20 mg of dexamethasone was administered weekly after the first week, and the entire 20-mg dose was given as a daratumumab pre-infusion medication on days when daratumumab was administered. Dosing of dexamethasone was otherwise split across days when KYPROLIS® was administered in both study arms.
§NYHA classification of heart failure III is defined as: Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea (shortness of breath). IV is defined as: Unable to carry out any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.7
BIW, twice a week; COPD, chronic obstructive pulmonary disease; CR, complete response; CrCl, creatinine clearance; DKd, carfilzomib + daratumumab + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group Performance Status; FEV1, forced expiratory volume in 1 second; Kd, carfilzomib + dexamethasone; LVEF, left ventricular ejection fraction; MRD, minimal residual disease; NYHA, New York Heart Association; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; R, randomization.
(View data)
Baseline disease characteristics and prior treatments were balanced between study arms2
*FISH analysis was conducted by the central lab. The high-risk group consisted of patients with the genetic subtypes t(4;14), t(14;16), or deletion 17p. The standard-risk group consisted of patients without cytogenetic abnormalities that are considered high risk. The unknown-risk group consisted of patients with FISH results that failed or were canceled.3
†Patients were considered refractory to a drug received in previous regimens if any of the following criteria were met: (1) best response to any regimen containing the drug was stable disease or progressive disease; (2) reason the drug was stopped was progression in any regimen; (3) date of relapse/progression was after start date and within 60 days after stop date of the drug in any regimen.3
ASCT, autologous stem cell transplant; DKd, carfilzomib + daratumumab + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group Performance Status; FISH, fluorescence in situ hybridization; ISS, International Staging System; IxRS, interactive voice-web response system; Kd, carfilzomib + dexamethasone.
DKd, carfilzomib + daratumumab + dexamethasone; Kd, carfilzomib + dexamethasone.
Please see accompanying full Prescribing Information.
Please see accompanying full Prescribing Information.
References: 1. Usmani S, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Lancet Oncol. 2022;23:65-76. 2. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 3. Dimopoulos M, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomized, multicentre, open-label, phase 3 study. Lancet. 2020;396:186-197. 4. Usmani SZ, Quach H, Mateos MV, et al. Final analysis of carfilzomib, dexamethasone, and daratumumab vs carfilzomib and dexamethasone in the CANDOR study. Blood Adv. 2023;7:3739-3748. 5. Dimopoulos M, Quach H, Mateos M-V, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Supplementary appendix. Lancet. 2020;396:186-197. 6. American Heart Association. Classes and Stages of Heart Failure. www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/classes-of-heart-failure. Accessed April 24, 2024.