Final analysis of carfilzomib, dexamethasone, and daratumumab vs carfilzomib and dexamethasone in the CANDOR study

Abstract

CANDOR (NCT03158688) is a phase 3, randomized, open-label trial comparing carfilzomib, daratumumab, and dexamethasone (KdD) vs carfilzomib and dexamethasone (Kd) in adults with relapsed/refectory multiple myeloma (RRMM) with 1 to 3 prior therapies. The CANDOR study met its primary end point of progression-free survival (PFS) in the primary analysis. Here, we report the final analysis of the study, including secondary end points and subgroup analyses thereof. The median follow-up was 50 months. Patients treated with KdD had higher minimal residual disease-negative (MRD-) achievement rates (28% vs 9%; odds ratio [OR], 4.22; 95% confidence interval [95% CI], 2.28-7.83) and MRD- complete response rates (22% vs 8%; OR, 3.55; 95% CI, 1.83-6.88) than those treated with Kd. Median PFS was 28.4 months for KdD vs 15.2 months for Kd (hazard ratio [HR], 0.64; 95% CI, 0.49-0.83). Median overall survival (OS) for KdD was 50.8 months vs 43.6 months for Kd (HR, 0.78 [0.60-1.03]; P = .042). Trends toward improved OS occurred in predefined subgroups, including patients refractory to lenalidomide (KdD, not reached vs Kd, 38.2 months; HR, 0.69 [0.43-1.11]) and refractory to proteasome inhibitor (KdD, 43.2 months vs Kd, 30.0 months; HR, 0.70 [0.45-1.09]), and there was significant improvement in patients with high-risk cytogenetics (KdD, 34.3 months vs Kd: 17.1 months; HR, 0.52 [0.29-0.94]). No new safety signals were identified. In summary, the final analysis of CANDOR confirmed the PFS benefit and showed a trend in OS benefit with KdD vs Kd. These findings reinforce KdD as a standard of care for RRMM, especially in clinically relevant patient subgroups. This trial was registered at www.clinicaltrials.gov as #NCT03158688.

Conflict of interest statement

Conflict-of-interest disclosure: S.Z.U. reports grants and personal fees from AbbVie, Amgen, Bristol Myers Squibb (BMS), Celgene, GlaxoSmithKline (GSK), Janssen, Merck, MundiPharma, Oncopeptides, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, and Takeda. H.Q. reports grants from Amgen, Celgene, GSK, and Karyopharm; consultancy and/or membership on an advisory committee from BMS, Celgene, GSK, Janssen, Karyopharm, and Takeda; receipt of study materials from Amgen, GSK, Karyopharm, and Sanofi; and leadership or fiduciary role with Amgen, BMS, and GSK. M.-V.M. reports consulting fees from Janssen, Celgene, Amgen, Takeda, AbbVie, GSK, Oncopeptides, Adaptive, Sanofi, Pfizer, Roche, and Bluebird Bio. O.L. reports honoraria and/or membership on the board of directors for Adaptive, Amgen, Celgene, Janssen, and Takeda, and membership on independent data monitoring committees for Merck and Theradex. X.L. reports honoraria from Sanofi, Takeda, Oncopeptides, Karyopharm, Amgen, Carsgen, Incyte, Novartis, Celgene, Janssen, BMS, Merck, GSK, and AbbVie. D.S. reports honoraria from and service on speakers bureaus for Novartis, Karyopharm, Janssen, BMS, Takeda, Amgen, and Celgene; consulting and membership on the boards of directors or advisory committees for Janssen, BMS, Takeda, Amgen, Celgene, and Celularity Scientific; and research funding from Janssen, BMS, Takeda, Amgen, and Celgene. K.W. reports consultancy for Janssen, Adaptive Biotech, Amgen, BMS, Sanofi, Takeda, Oncopeptides, Karyopharm, GSK, and Celgege; honoraria from Janssen, Adaptive Biotech, Amgen, BMS, Celgene, Sanofi, Takeda, and GSK; and research funding from Janssen, Amgen, Celgene, and Sanofi. X.S. reports employment with Parexel International. C.L. reports employment with and stockholdings in Amgen. M.D. reports consulting fees from Janssen, Amgen, BMS, Takeda, and BeiGene; honoraria from BeiGene, Janssen, Amgen, BMS, Takeda; and research funding from BMS, Janssen, Amgen, Takeda, and BeiGene.

© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Graphical abstract

Figure 1.

Patient flowchart. ∗Category includes patients who discontinued study treatment at study closure per the protocol.

Figure 2.

Kaplan-Meier estimates of OS.

Figure 3.

Prespecified subgroup analyses of OS. CrCl, creatinine clearance.