ABSTRACT
Introduction: The randomized, open-label, multicenter, phase 3 CANDOR study compared carfilzomib, dexamethasone, and daratumumab (KdD) to carfilzomib and dexamethasone (Kd) in patients with multiple myeloma who have relapsed after 1-3 prior lines of therapy (ClinicalTrials.gov, NCT03158688). In the previously reported primary analysis (Dimopoulos et al, Lancet 2020), a significant progression-free survival (PFS) benefit was demonstrated in patients treated with KdD vs patients treated with Kd (hazard ratio [HR], 0.63 [95% CI, 0.46-0.85];two-sided P=0.0027). However, after a median follow-up of 16.9 months, median PFS was not reached in the KdD arm. Here, we report updated efficacy and safety outcomes from the CANDOR study. Methods: Adult patients with relapsed or refractory multiple myeloma (RRMM) received 28-day cycles of KdD or Kd (randomized 2:1). In the primary analysis, PFS was the primary endpoint and overall survival (OS) a key secondary endpoint. In this prespecified interim OS analysis, statistical testing was based on the actual number of OS events observed by the data cutoff (approximately 36 months after enrollment of the first patient);PFS was summarized descriptively. Disease progression was determined locally by investigators in an unblinded manner and centrally by the sponsor using a validated computer algorithm (Onyx Response Computer Algorithm [ORCA]) in a blinded manner. PFS and OS were compared between the KdD and Kd arms using a stratified log-rank test, and HRs were estimated by a stratified Cox proportional-hazards model. Results: Patients were randomized to KdD (n = 312) and Kd (n = 154). Of all randomized patients, median age was approximately 64 years;42% received previous lenalidomide, and 33% were lenalidomide refractory;90% received previous bortezomib, and 29% were bortezomib refractory. At the data cutoff date of June 15, 2020, 199 (63.8%) patients in the KdD arm and 88 (57.1%) in the Kd arm remained on study. Among patients treated with KdD and Kd, 140 (44.9%) and 85 (55.2%) had PFS events, respectively;median follow-up was 27.8 months (KdD) and 27.0 months (Kd). Median PFS by ORCA was 28.6 months for the KdD arm versus 15.2 months for the Kd arm (HR, 0.59 [95% CI, 0.45-0.78];Figure). OS data were not mature and will be updated at a future prespecified analysis. Median treatment duration was 79.3 weeks with KdD versus 40.3 weeks with Kd. Grade ≥3 adverse events (AEs) occurred in 87.0% and 75.8% of patients in the KdD and Kd arms, respectively, and fatal AEs occurred in 8.8% and 4.6%;one fatal AE in the KdD arm (due to arrhythmia) and one fatal AE in the Kd arm (due to COVID-19 pneumonia) had occurred since the primary analysis. Carfilzomib treatment discontinuation rates due to AEs were 26.0% with KdD and 22.2% with Kd. Exposure-adjusted AE rates per 100 patient years were: 171.2 and 151.9 for grade ≥3 AEs and 6.9 and 5.6 for fatal AEs in the KdD and Kd arms, respectively. Updated data by key subgroups will be presented. Conclusion: With approximately 11 months of additional follow-up, a 13.4-month improvement in median PFS was observed in patients treated with KdD (28.6 months) versus patients treated with Kd (15.2 months;HR, 0.59 [95% CI, 0.45-0.78]). Safety was consistent with previously reported results. KdD continues to show a favorable benefit-risk profile and represents an efficacious treatment option for patients with RRMM. [Formula presented] Disclosures: Dimopoulos: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau;BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau;Celgene: Consultancy, Ho oraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau. Quach: GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy;Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees;Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding;GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria. Mateos: EDOMundipharma: Consultancy;Adaptive: Consultancy;Pharmamar: Consultancy;GlaxoSmithKline: Consultancy;AbbVie: Consultancy;Takeda: Consultancy;Amgen: Consultancy;Celgene: Consultancy;Janssen: Consultancy. Landgren: Pfizer: Consultancy, Honoraria;Merck: Other;Cellectis: Consultancy, Honoraria;Juno: Consultancy, Honoraria;Glenmark: Consultancy, Honoraria, Research Funding;BMS: Consultancy, Honoraria;Binding Site: Consultancy, Honoraria;Celgene: Consultancy, Honoraria, Research Funding;Pfizer: Consultancy, Honoraria;Karyopharma: Research Funding;Merck: Other;Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding;Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding;Glenmark: Consultancy, Honoraria, Research Funding;Juno: Consultancy, Honoraria;Seattle Genetics: Research Funding;Cellectis: Consultancy, Honoraria;Seattle Genetics: Research Funding;Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding;BMS: Consultancy, Honoraria;Adaptive: Consultancy, Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;Binding Site: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding;Karyopharma: Research Funding. Leleu: Incyte: Honoraria;Merck: Honoraria;Novartis: Honoraria;Amgen: Honoraria;GSK: Honoraria;Sanofi: Honoraria;BMS-celgene: Honoraria;Janssen: Honoraria;Oncopeptide: Honoraria;AbbVie: Honoraria;Carsgen: Honoraria;Karyopharm: Honoraria. Siegel: Janssen: Consultancy, Honoraria, Speakers Bureau;Merck: Consultancy, Honoraria, Speakers Bureau;Amgen: Consultancy, Honoraria, Speakers Bureau;Celulatiry: Consultancy;Karyopharma: Consultancy, Honoraria;Takeda: Consultancy, Honoraria, Speakers Bureau;BMS: Consultancy, Honoraria, Speakers Bureau. Weisel: Takeda: Consultancy, Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Karyopharm: Consultancy, Honoraria;Adaptive: Consultancy, Honoraria;Bristol-Myers Squibb: Consultancy, Honoraria;GlaxoSmithKline: Honoraria;Sanofi: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;Abbvie: Consultancy, Honoraria;Roche: Consultancy, Honoraria. Gavriatopoulou: Takeda: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Genesis Pharma: Consultancy, Honoraria;Karyopharm: Consultancy, Honoraria;Amgen: Consultancy, Honoraria. Oriol: Janssen: Consultancy;Celgene: Consultancy, Speakers Bureau;Amgen: Consultancy, Speakers Bureau. Rabin: Janssen, BMS/Celgene, Takeda, Karyopharm, Amgen: Consultancy;Janssen, BMS/Celgene, Takeda: Other: Travel;Jansse, BMS/Celgene, Takeda: Speakers Bureau. Nooka: GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding;Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding;Spectrum Pharmaceuticals: Consultancy;Celgene: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding;Oncopeptides: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Research Funding;Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria;Adaptive Technologies: Consultancy, Honoraria;Takeda: Consultancy, Honoraria, Research Funding. Ding: Amgen: Current Employment. Zahlten-Kumeli: Amgen: Current Employment, Current equity holder in publicly-traded compan . Usmani: Celgene: Other;GSK: Consultancy, Research Funding;Pharmacyclics: Research Funding;Array Biopharma: Research Funding;Seattle Genetics: Consultancy, Research Funding;Merck: Consultancy, Research Funding;Incyte: Research Funding;SkylineDX: Consultancy, Research Funding;Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding;Sanofi: Consultancy, Honoraria, Research Funding;Abbvie: Consultancy;BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding;Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding;Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding.