A.R.R.O.W.2: Once- vs twice-weekly carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma

Twice-weekly carfilzomib (27 mg/m2) plus lenalidomide and dexamethasone (KRd27) is a standard-of-care in relapsed/refractory multiple myeloma (RRMM). Once-weekly carfilzomib regimens have shown clinical benefits with improved patient convenience. This open-label, phase 3, multicenter, randomized study aimed to demonstrate noninferiority of the overall response rate (ORR) for once-weekly carfilzomib (56 mg/m2) plus Rd (KRd56) vs twice-weekly KRd27 in RRMM. A total of 454 patients were randomized (1:1) to receive carfilzomib as once-weekly 30-minute infusions of 56 mg/m2 (KRd56; n=228) or twice-weekly 10-minute infusions of 27 mg/m2 (KRd27; n=226). Baseline characteristics were balanced between groups. ORR was 82.5% (95% confidence interval [CI], 76.9‒87.2) in the once-weekly group vs 86.3% (95% CI, 81.1‒90.5) in the twice-weekly group (risk ratio, 0.954 [95% CI, 0.882‒1.032]) and did not meet the threshold for statistical significance of noninferiority (P=0.0666). Complete response or better was obtained in 46.9% of patients in the once-weekly arm and 36.3% in the twice-weekly arm. The proportions of patients who achieved complete response and were also assessed negative for minimal residual disease were 21.5% and 18.1%, respectively (odds ratio, 1.235 [95% CI, 0.775‒1.970]). Progression-free survival was comparable between groups (hazard ratio, 0.945 [95% CI, 0.617‒1.447]). The safety profile was similar for both groups. In conclusion, although statistical significance for noninferiority of ORR was not achieved, the efficacy and safety of once-weekly KRd56 were similar to those of twice-weekly KRd27 and once-weekly KRd56 may be an effective and convenient treatment option for patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT03859427.