Once-weekly (70 mg/m²) vs twice-weekly (56 mg/m²) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials

Combination of carfilzomib with dexamethasone (Kd) is approved for use in relapsed and/or refractory multiple myeloma (RRMM), with carfilzomib administered twice weekly at 56 mg/m² (Kd56 BIW) or once weekly at 70 mg/m² (Kd70 QW). Post hoc cross-trial comparisons were performed to compare efficacy and safety profiles of Kd70 QW vs Kd56 BIW dosing schedules using data from three trials of patients with RRMM: A.R.R.O.W., CHAMPION-1, and ENDEAVOR. To select for comparable patient populations, side-by-side efficacy and safety comparisons were performed in subgroups of patients with 2-3 prior lines of therapy who were not refractory to bortezomib. The overall response rate (ORR) was 69.9% (95% confidence interval [CI], 61.7-77.2) for Kd70 QW and 72.4% (95% CI, 65.9-78.2) for Kd56 BIW. Median progression-free survival (PFS) was 12.1 months (95% CI, 8.4-14.3) for Kd70 QW and 14.5 months (95% CI, 10.2—not evaluable) for Kd56 BIW. Frequency of grade ≥ 3 adverse events (AEs) was 67.6% for Kd70 QW and 85.3% for Kd56 BIW. Regression analyses (adjusting for prognostic factors) of all patients in the trials who received Kd70 QW vs Kd56 BIW estimated a PFS hazard ratio of 0.91 (95% CI, 0.69-1.19; P =.47) and an ORR odds ratio of 1.12 (95% CI, 0.74-1.69; P =.61). These results suggest that Kd70 QW has a comparable efficacy profile compared with Kd56 BIW and represents a convenient and well-tolerated treatment for patients with RRMM.