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1885 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

Myeloma: Therapy, excluding Transplantation
Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
Saturday, December 9, 2017, 5:30 PM-7:30 PM
Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Ruben Niesvizky, MD1, Heinz Ludwig, MD2, Andrew Spencer, MD3, Hartmut Goldschmidt, MD 4, Tomas Pika5*, Maria-Victoria Mateos6, Meletios A. Dimopoulos7, Lifen Zhou8*, Amy S. Kimball8* and Thierry Facon, MD9*

1Division of Hematology and Oncology, Weill Cornell Medicine /New York Presbyterian Hospital, New York, NY
2Wilhelminen Cancer Research Institute, Vienna, Austria
3Alfred Health-Monash University, Melbourne, Canada
4University Hospital of Heidelberg, Heidelberg, Germany
5University Hospital Olomouc, Olomouc, Czech Republic
6University Hospital of Salamanca, Salamanca, Spain
7National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
8Amgen, Inc., Thousand Oaks, CA
9Centre Hospitalier Regional Universitaire (CHRU) Lille, Hopital Huriez, Lille, France

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., <65, 65–74, and ≥75 years of age) using an unstratified Cox proportional hazards model.

Results: The ITT population included 929 patients enrolled in the study (<65 years: Kd56, n=223; Vd, n=210; 65–74 years: Kd56, n=164; Vd, n=189; ≥75 years: Kd56, n=77; Vd, n=66). OS was improved with Kd56 vs Vd within each age subgroup (<65 years: median, 47.6 months vs 41.9 months [HR, 0.847; 95% CI, 0.634–1.132]; 65–74 years: median, not estimable vs 37.0 months [HR, 0.706; 95% CI, 0.508–0.981]; ≥75 years: median, 42.4 months vs 25.9 months [HR, 0.841; 95% CI, 0.522–1.355]) (Table). Kaplan-Meier OS curves by age are shown in the Figure. In the safety population (n=919), the median duration of treatment was longer with Kd56 than with Vd within each age subgroup (<65 years: median, 49.0 weeks vs 27.0 weeks; 65–74 years: 49.9 weeks vs 27.6 weeks; ≥75 years: 43.3 weeks vs 20.6 weeks). Rates of any-grade adverse events (AEs) and grade ≥3 AEs of interest are shown in the Table. Grade ≥3 hypertension, dyspnea, cardiac failure, acute renal failure, and cardiac ischemia were generally more common with Kd56 vs Vd within each age subgroup, whereas grade ≥3 peripheral neuropathy occurred more often with Vd vs Kd56 within each subgroup (Table). AEs were not adjusted for exposure.

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.

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. 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; Novartis: Consultancy, Honoraria; 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. Zhou: Amgen: Employment, Equity Ownership. Kimball: Amgen: Employment, Equity Ownership. Facon: Amgen, Celgene: Speakers Bureau.

*signifies non-member of ASH