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.

BACKGROUND

Despite recent advances in therapeutic options, there remains an unmet need for treating patients with relapsed or refractory multiple myeloma, especially in those previously exposed or refractory to lenalidomide. This updated efficacy and safety analysis from the phase 3 CANDOR study compared carfilzomib, daratumumab, and dexamethasone (KdD) with carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma.

METHODS

In this updated analysis of the randomised, multicentre, open-label, phase 3 CANDOR study, patients (aged ≥18 years) with relapsed or refractory multiple myeloma, at least a partial response to between one and three previous therapies, and Eastern Cooperative Oncology Group performance status of 0-2, were recruited from 102 medical centres globally and randomly assigned (2:1) by interactive voice or web response software to receive KdD or Kd. Participants were stratified by disease stage, previous proteasome inhibitor or anti-CD38 antibody exposure, and number of previous therapies. All patients received intravenous infusions of carfilzomib twice per week at 56 mg/m

FINDINGS

Between June 13, 2017, and June 25, 2018, 466 patients were enrolled, of whom 312 received KdD and 154 received Kd. At data cutoff (June 15, 2020), median follow-up was 27·8 months (IQR 25·6-29·5) for KdD and 27·0 months (13·2-28·6) for Kd. Median progression-free survival was 28·6 months (95% CI 22·7-not estimable [NE]) in the KdD group and 15·2 months (11·1-19·9) in the Kd group (hazard ratio 0·59 [95% CI 0·45-0·78], log-rank p<0·0001). Treatment-emergent adverse events in the safety population were consistent with the primary analysis. Grade 3 or worse treatment-emergent adverse events occurred in 268 (87%) patients in the KdD group and 116 (76%) in the Kd group; most commonly thrombocytopenia (76 [25%] vs 25 [16%], respectively), hypertension (65 [21%] vs 23 [15%]), pneumonia (54 [18%] vs 14 [9%]), and anaemia (53 [17%] vs 23 [15%]). Serious adverse events occurred in 194 (63%) patients with KdD and 76 (50%) with Kd. Adverse events leading to death occurred in 27 (9%) patients in the KdD group and seven (5%) in the Kd group; most commonly septic shock (five [2%] vs one (1%]) and pneumonia (four [1%] vs none). No new treatment-related deaths have occurred since the primary analysis.

INTERPRETATION

A clear, maintained progression-free survival benefit of KdD over Kd with longer follow-up was confirmed, making KdD an emerging standard-of-care for patients with relapsed or refractory multiple myeloma.

FUNDING

Amgen and Janssen.

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests SZU reports grants and personal fees from Amgen, Celgene, Sanofi, Seattle Genetics, Janssen, Takeda, SkylineDX, Merck, and GlaxoSmithKline; personal fees from AbbVie, MundiPharma, and Oncopeptides; and grants from Bristol-Myers Squibb and Pharmacyclics. HQ reports grants (to institution) from Celgene, Amgen, GlaxoSmithKline, and Karyopharm; consultancy or membership (or both) on an advisory committee from Takeda, GlaxoSmithKline, Karyopharm, Celgene, and Janssen; membership on an advisory committee from Takeda, GlaxoSmithKline, Karyopharm, Bristol-Myers Squibb, and Janssen; leadership or fiduciary role for GlaxoSmithKine, Bristol-Myers Squibb, and Amgen; and receipt of free drug for investigator-initiated study from GlaxoSmithKline, Sanofi, Amgen, and Karyopharm. M-VM reports consulting fees from Janssen, Celgene, Amgen, Takeda, AbbVie, GlaxoSmithKline, Oncopeptides, Adaptive, Sanofi, Pfizer, Roche, and Bluebird-bio. OL reports honoraria or membership (or both) on the board of directors for Adaptive, Amgen, Celgene, Janssen, and Takeda; and membership on independent data monitoring committees for Merck and Theradex. XL reports honoraria from Sanofi, Takeda, Oncopeptide, Karyopharm, Amgen, Carsgen, Incyte, Novartis, Celgene, Janssen, Bristol-Myers Squibb, Merck, GlaxoSmithKline, and AbbVie. DS reports honoraria fees and speakers' bureau fees for Novartis, Karyopharm, Janssen, Bristol-Myers Squibb, Takeda, Amgen, and Celgene; consulting fees and membership on the Board of Directors or advisory committees for Janssen, Bristol-Myers Squibb, Takeda, Amgen, Celularity, and Celgene; research funding from Janssen, Bristol-Myers Squibb, Takeda, Amgen, and Celgene. KW reports consultancy fees from Janssen, Adaptive Biotech, Amgen, Bristol-Myers Squibb, Sanofi, Takeda, Oncopeptides, Karyopharm, GlaxoSmithKline, and Celgene; honoraria for speakers' bureaus from Janssen, Adaptive Biotech, Amgen, Bristol-Myers Squibb, Celgene, Sanofi, Takeda, and GlaxoSmithKline; and grants or contracts (to institution) from Janssen, Amgen, Celgene, and Sanofi. AO reports consultancy fees from Celgene/Bristol Myers Squibb, Sanofi, Amgen, and GlaxoSmithKline; speakers bureau fees from Celgene and Amgen; and fees for participation on advisory boards for Celgene/Bristol Myers Squibb, Sanofi, Amgen, and GlaxoSmithKline. NR reports consulting fees from Celgene, Amgen, Takeda, and Karyopharm; payment or honoraria for speakers' bureaus from Celgene, Janssen, and Takeda; travel support from Celgene, Janssen, and Takeda; and participation on advisory boards for Celgene, Amgen, Takeda, and Karyopharm. AN reports consultancy or membership (or both) on an advisory committee for Bristol Myers Squibb, Adaptive Biotech, Amgen, Celgene, Sanofi, Oncopep, Takeda, Karyopharm, GlaxoSmithKline, and Janssen. MQ reports employment with and stockholdings of Janssen R&D. MB reports advisory board or speakers bureau fees from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Oncopeptides, Sanofi, and Takeda. AJ reports honoraria for advisory board participation and consulting from AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Karyopharm, and Sanofi-Aventis. BD made contributions to this publication while employed by Amgen. AZ-K and AY report employment with and equity ownership in Amgen. MD reports consulting fees from Janssen, Amgen, Bristol-Myers Squibb, Takeda, and Beigene; payment or honoraria for speakers bureaus from Beigene, Janssen, Amgen, Bristol-Myers Squibb, and Takeda; and grants or contracts from Bristol-Myers Squibb, Janssen, Amgen, Takeda, and Beigene. MG declares no competing interests.