Once-Weekly Vs Twice-Weekly Carfilzomib Dosing Plus Dexamethasone in Patients with Relapsed and Refractory Multiple Myeloma (RRMM): Results of the Randomized Phase 3 Study A.R.R.O.W.
Authors: Maria-Victoria Mateos , Philippe Moreau , James R. Berenson , Katja Weisel , Antonio Lazzaro , Kevin Song , Meletios A. Dimopoulos , Mei Huang , Anita Zahlten-Kumeli , A. Keith Stewart
The objective of the study was to develop a more convenient K regimen. Once-weekly K plus dexamethasone (d) was assessed in the phase 1/2 CHAMPION-1 study, establishing a maximum tolerated dose of K 20/70 mg/m2 for RRMM pts.
The results demonstrated a median PFS of 11.2 mo for the once-weekly vs 7.6 mo for the twice-weekly dosing (hazard ratio = 0.69; 1-sided P=0.0014). ORR was 62.9% for the once-weekly vs 40.8% for the twice weekly dosing (P<0.0001) and 7.1% vs 1.7% had a complete response or better.
Grade ≥3 adverse events (AEs) occurred in 67.6% (once-weekly) and 61.7% (twice-weekly). Treatment-related grade 5 AEs occurred in 5 pts (2.1%) (once-weekly) and 2 pts (0.9%) (twice-weekly). The incidence of grade ≥3 hypertension and cardiac failure (once- vs twice-weekly) was 5.9% vs 5.5% and 2.9% vs 4.3%, respectively.
The authors concluded that once-weekly Kd at 20/70 mg/m2 significantly improved PFS and ORR vs twice-weekly Kd at 20/27 mg/m2. while demonstrating comparable safety.