Overall Survival of Relapsed/Refractory Multiple Myeloma Patients Treated with Carfilzomib and Dexamethasone Vs Bortezomib and Dexamethasone: Results from the Phase 3 Endeavor Study According to Age Subgroup

Abstract

Abstract Background: Elderly patients with multiple myeloma are a challenging population to treat, and there is a need for effective treatment options. Carfilzomib, a selective proteasome inhibitor, is approved in the United States and other countries for the treatment of relapsed or refractory multiple myeloma (RRMM). A subgroup analysis of interim results from the randomized, phase 3 ENDEAVOR study showed that carfilzomib (56 mg/m2) and dexamethasone (Kd56) resulted in longer median progression-free survival (PFS) and higher overall response rates (ORRs) than bortezomib and dexamethasone (Vd) in patients with RRMM, regardless of age (Table; Ludwig et al, Leuk Lymphoma . 2017;58:2501-2504). Mature overall survival (OS) data has recently been reported from ENDEAVOR and demonstrated that Kd56 resulted in statistically and clinically significant improvement in OS compared with Vd in the intention-to-treat (ITT) population (median, 47.6 months vs 40.0 months; hazard ratio [HR], 0.791; 95% confidence interval [CI], 0.648-0.964; 1-sided P=0.0100; Dimopoulos et al, Lancet Oncol . In press). Here, we report a subgroup analysis from ENDEAVOR to evaluate OS and updated safety outcomes by age. Methods: Adults with RRMM who received 1-3 prior regimens were eligible for the ENDEAVOR trial. Patients treated with Kd56 received carfilzomib (30-min intravenous [IV] infusion) on days (D) 1, 2, 8, 9, 15, and 16 (20 mg/m2 on D1, 2 [cycle 1]; 56 mg/m2 thereafter) and dexamethasone (20 mg) on D1, 2, 8, 9, 15, 16, 22, and 23 of 28-day cycles. In the Vd arm, patients received bortezomib (1.3 mg/m2; IV or subcutaneously) on D1, 4, 8, and 11 and dexamethasone (20 mg) on D1, 2, 4, 5, 8, 9, 11, and 12 of 21-day cycles. Patients were treated until disease progression, withdrawal of consent, or unacceptable toxicity. OS was compared between treatment arms in patients grouped according to age (i.e., Results: The ITT population included 929 patients enrolled in the study ( Conclusions: Clinically meaningful improvements in OS were observed with Kd56 compared with Vd across all age groups examined, including patients aged ≥75 years. The safety results were comparable to those reported in the age subgroup analysis of the PFS interim results for ENDEAVOR. Overall, these data support the favorable benefit-risk profile of Kd56 in patients with RRMM, regardless of age. Download : Download high-res image (187KB) Download : Download full-size image Disclosures Niesvizky: Janssen: Consultancy; Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy. Ludwig: Celgene: Speakers Bureau; Janssen-Cilag: Consultancy, Speakers Bureau; AMGEN: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Bristol-Meyers: Speakers Bureau; Takeda: Research Funding, Speakers Bureau. Spencer: Amgen: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Goldschmidt: Chugai: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Morphosys: Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Research Funding, Speakers Bureau. Mateos: Takeda: Consultancy, Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Consultancy, Honoraria. Dimopoulos: Genesis Pharma: Research Funding; Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology: Consultancy, Honoraria, Other: Advisory Committee: Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology; Novartis: Consultancy, Honoraria. Zhou: Amgen: Employment, Equity Ownership. Kimball: Amgen: Employment, Equity Ownership. Facon: Amgen, Celgene: Speakers Bureau.