Once-weekly vs. twice-weekly carfilzomib dosing in a subgroup of Japanese relapsed and refractory multiple myeloma patients from a randomized phase 3 trial (A.R.R.O.W.) and comparison with ENDEAVOR

Takezako, Naoki; Shibayama, Hirohiko; Handa, Hiroshi; Hagiwara, Shotaro; Ozaki, Shuji; Suzuki, Kenshi; Kosugi, Hiroshi; Ri, Masaki; Sugiura, Isamu; Choi, Ilseung; Miyamoto, Toshihiro; Iida, Shinsuke

A.R.R.O.W. evaluated the superiority of once-weekly carfilzomib plus dexamethasone (Kd) 20/70 mg/m(2) vs. twice-weekly Kd 20/27 mg/m(2) based on progression-free survival (PFS) in relapsed and/or refractory multiple myeloma patients. Forty Japanese patients (once-weekly arm, n = 26; twice-weekly arm, n = 14) were randomized in A.R.R.O.W. In the Japanese subgroup of A.R.R.O.W., median PFS was 14.8 months (95% confidence interval [CI], 7.5–not evaluable [NE]) and 9.7 months (95% CI, 3.8–NE) in the once- and twice-weekly arms, respectively. The overall response rate (ORR) was 73.1% (19/26; 95% CI, 52.2–88.4) and 57.1% (8/14; 95% CI, 28.9–82.3) in each arm. The adverse events (AEs) incidence was 100% in both arms. Grade ≥ 3 AE incidence was 80.8% (21/26) and 78.6% (11/14) in each arm. Two fatal treatment-related AEs (acute lung injury and acute respiratory distress syndrome) occurred in the once-weekly arm. In exploratory unadjusted analyses of A.R.R.O.W. (once-weekly Kd 20/70 mg/m(2)) vs. ENDEAVOR (twice-weekly Kd 20/56 mg/m(2)), median PFS was 14.8 months vs. NE due to not yet being reached, and ORR was 73.1% (19/26) vs. 42.9% (3/7). In the Japanese subgroup, once-weekly Kd tended to improve ORR vs. twice-weekly Kd. Results from A.R.R.O.W. tended to be consistent with results from ENDEAVOR. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12185-020-03013-6) contains supplementary material, which is available to authorized users.