Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study

Twice‐weekly carfilzomib (27 mg/m(2)) with lenalidomide‐dexamethasone (KRd) is a standard‐of‐care in relapsed or refractory multiple myeloma (RRMM). This phase 1b study evaluated KRd with once‐weekly carfilzomib in RRMM. Patients received carfilzomib (30‐minute infusion; 56 or 70mg/m(2)) on days 1, 8, and 15; lenalidomide 25 mg on days 1‐21; and dexamethasone 40 mg on days 1, 8, 15, and 22 (day 22 omitted for cycles 9+) of 28‐day cycles. Primary objective was safety/tolerability; efficacy was a secondary objective. Fifty‐six RRMM patients enrolled: 22 during dose evaluation (56‐mg/m(2), n = 10; 70‐mg/m(2), n = 12) and 34 during dose expansion (all initiated dosing at 70 mg/m(2)). After 2 fatal adverse events (AEs) during 70‐mg/m(2) dose expansion, dosage reduction to 56 mg/m(2) was permitted. Results are presented for carfilzomib 56‐mg/m(2) (n = 10) and 70‐mg/m(2) groups (dose evaluation/expansion; n = 46). Median carfilzomib dose was 53.2 mg/m(2) (56‐mg/m(2) group) and 62.4 mg/m(2) (70‐mg/m(2) group). Grade ≥3 AE rates were 70.0% (56 mg/m(2)) and 69.6% (70 mg/m(2)). Overall response rates were 90.0% (56 mg/m(2)) and 89.1% (70 mg/m(2)); ≥very good partial response rates were 50.0% (56 mg/m(2)) and 73.9% (70 mg/m(2)). Once‐weekly KRd was active with acceptable toxicity in RRMM, supporting further evaluation of this regimen.