Efficacy and safety of carfilzomib-based regimens in frail patients with relapsed and/or refractory multiple myeloma

Abstract

Frailty is most prevalent among elderly multiple myeloma (MM) patients, and frail patients have a higher risk of poor outcomes due to reduced performance status or comorbidities. This post hoc analysis assessed efficacy and safety of carfilzomib combinations in frail patients with relapsed and/or refractory MM from the phase 3 ASPIRE (carfilzomib [27 mg/m2]-lenalidomide-dexamethasone [KRd27] vs lenalidomide-dexamethasone [Rd]), ENDEAVOR (carfilzomib [56 mg/m2]-dexamethasone [Kd56] vs bortezomib-dexamethasone [Vd]), and ARROW (once-weekly carfilzomib [70 mg/m2]-dexamethasone [Kd70] vs carfilzomib [27 mg/m2]-dexamethasone [Kd27]) studies. A frailty algorithm incorporating age, Charlson comorbidity index, and performance status classified patients as fit, intermediate, or frail. Results are presented for frail patients (ASPIRE, n = 196; ENDEAVOR, n = 330; ARROW, n = 141). In ASPIRE, median progression-free survival (PFS) (hazard ratio; 95% confidence interval) was 24.1 (KRd27) vs 15.9 months (Rd) (0.78; 0.54-1.12); median overall survival (OS) was 36.4 vs 26.2 months (0.79; 0.57-1.08). In ENDEAVOR, median PFS was 18.7 (Kd56) vs 6.6 months (Vd) (0.50; 0.36-0.68); median OS was 33.6 vs 21.8 months (0.75; 0.56-1.00). In ARROW, median PFS was 10.3 (once-weekly Kd70) vs 6.6 months (twice-weekly Kd27) (0.76; 0.49-1.16). In all 3 studies, rates of grade ≥3 treatment-emergent adverse events were consistent with those observed in the primary studies. The ASPIRE, ENDEAVOR, and ARROW primary analyses demonstrated favorable benefit-risk profiles with carfilzomib-containing regimens compared with controls. Across clinically relevant subgroups, including those by frailty status, consistent efficacy and safety were observed with KRd27, Kd56, and weekly Kd70, and treatment with these regimens should not be restricted by frailty status.

Conflict of interest statement

Conflict-of-interest disclosure: T.F. served as a consultant or advisor for Janssen, Celgene, Amgen, Takeda, Karyopharm, and Oncopeptides and served on the speakers’ bureau for Janssen, Celgene, and Takeda. R.N. served as a consultant for Celgene, Amgen, Takeda, Janssen, and BMS. M.-V.M. received honoraria from Celgene, Janssen, Takeda, Amgen, and AbbVie. D.S. received honoraria and consulting/advisory role fees for Celgene, Amgen, Merck, Janssen, BMS, Takeda, and Karyopharm; participated in the speakers’ bureau for Celgene, Amgen, Merck, Janssen, BMS, and Takeda; and received research funding from Celgene. C.R. received honoraria from, and had travel/accommodations/other expenses paid by, Celgene and BMS. S.B. served as a consultant for Takeda; received honoraria from Amgen, Takeda, Janssen, Celgene, and BMS; and served as a member of the board of directors/advisory committees for Janssen and Celgene. K. Weisel received honoraria from Amgen, Celgene, BMS, Janssen, and Takeda; received research funding from Amgen, Celgene, Janssen, and Sanofi; and served as a consultant for Amgen, Adaptive Biotech, Sanofi, Celgene, BMS, Juno, Janssen, Takeda. P.J.H. received an honorarium from Janssen-Cilag for an advisory board. H.L. served as a consultant or advisor for PharmaMar; served on the speakers’ bureau for Takeda, Amgen, BMS, Janssen, and Celgene; and received research funding from Takeda and Amgen. S.K. reports non-paid consulting and advisory board roles for AbbVie, Celgene, Janssen, Kite Pharma, Merck, and Takeda. K. Wang, M.O., Z.Y., Z.K., K.M., A.G., and C.T. are employees of and own stock in Amgen, Inc. M.A.D. received honoraria from Celgene, BMS, Janssen, Takeda, and Amgen.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Kaplan-Meier curves for PFS and OS in the frail and fit subgroups in ASPIRE. PFS (A) and OS (B) were assessed in the intent-to-treat population.

Figure 2.

Kaplan-Meier curves for PFS and OS in the frail and fit subgroups in ENDEAVOR. PFS (A) and OS (B) were assessed in the intent-to-treat population. NE, not estimable.

Figure 3.

Kaplan-Meier curves for PFS in the fit and frail subgroups in ARROW. PFS was assessed in the intent-to-treat population.