Carfilzomib (K) in relapsed and refractory multiple myeloma (RRMM): Frailty subgroup analysis from phase III ASPIRE and ENDEAVOR.

person Thierry Facon Hôpital Claude Huriez, Lille, France info_outline Thierry Facon, Ruben Niesvizky, Katja Weisel, Sara Bringhen, P. Joy Ho, Mihaela Obreja, Zhao Yang, Zandra Karina Klippel, Julie Blaedel, Khalid Mezzi, David Samuel DiCapua Siegel

Authors person Thierry Facon Hôpital Claude Huriez, Lille, France info_outline Thierry Facon, Ruben Niesvizky, Katja Weisel, Sara Bringhen, P. Joy Ho, Mihaela Obreja, Zhao Yang, Zandra Karina Klippel, Julie Blaedel, Khalid Mezzi, David Samuel DiCapua Siegel Organizations Hôpital Claude Huriez, Lille, France, Weill Cornell Medicine, New York, NY, Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy, Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia, Amgen, Inc., Thousand Oaks, CA, Hackensack University Medical Center, Hackensack, NJ Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: K-based regimens improved progression-free survival (PFS) and overall survival (OS) in RRMM patients (pts) in ASPIRE (K [27 mg/m 2 ]-lenalidomide-dexamethasone [KRd] vs Rd) and ENDEAVOR (K [56 mg/m 2 ]-dexamethasone [Kd56] vs bortezomib-dexamethasone [Vd]), regardless of age. Frailty scores have been developed based on age, comorbidities, and functional status (Palumbo Blood 2015;125:2068–74; Facon Blood 2015;126:4239). We assessed post hoc pt outcomes by frailty status. Methods: PFS, OS, and safety were assessed by treatment arm and frailty score (based on age, medical history-derived Charlson Comorbidity Index, and ECOG performance status); frailty scores: 0 = fit, 1 = intermediate (int), and ≥2 = frail. Results: Pt frailty status was balanced between treatment arms in ASPIRE and ENDEAVOR. Median PFS and OS were longer with K-based regimens vs controls in ASPIRE and ENDEAVOR across frailty subgroups (Table). Rates of treatment-emergent adverse events are summarized in the Table. Conclusions: Kd56 and KRd consistently improved outcomes vs Vd and Rd, respectively, in all frailty subgroups as defined by the algorithm above. These findings support the favorable benefit-risk profile of KRd and Kd56 regardless of frailty score. Clinical trial information: NCT01080391 and NCT01568866 ASPIRE ENDEAVOR Fit Int Frail Fit Int Frail KRd, n = 115 Rd, n = 114 KRd, n = 149 Rd, n = 138 KRd, n = 93 Rd, n = 103 Kd56, n = 110 Vd, n = 121 Kd56, n = 168 Vd, n = 169 Kd56, n = 168 Vd, n = 162 Median PFS, mos 31.4 18.9 29.6 18.5 24.1 15.9 NE 12.1 16.8 9.9 18.7 6.6 HR (95% CI) 0.70 0.70 0.78 0.51 0.54 0.50 (0.49– 1.01) (0.50– 0.96) (0.54– 1.12) (0.33– 0.79) (0.39– 0.75) (0.36– 0.68) Median OS, mos 55.6 43.3 48.3 47.9 36.4 26.2 NE 42.2 NE 41.9 33.6 21.8 HR (95% CI) 0.71 0.94 0.79 0.65 0.89 0.75 (0.51– 0.99) (0.70– 1.27) (0.57– 1.08) (0.40– 1.06) (0.64– 1.24) (0.56– 1.00) Any grade AE (grade ≥3), % a 99 99 99 96 99 100 100 99 98 99 100 99 AE leading to a (89) (84) (88) (79) (94) (94) (83) (64) (81) (71) (85) (79) treatment discontinuation, % 33 30 36 23 37 43 26 29 27 22 33 30 a Based on safety population n: ASPIRE (KRd, Rd): fit (115, 114), int (147, 135), frail (92, 100); ENDEAVOR (Kd56, Vd): fit (110, 119), int (167, 165), frail (168, 159). NE, not estimable.