An open-label phase 2 study treating patients with first or second relapse of multiple myeloma with carfilzomib,...

Once-weekly carfilzomib at 56 mg/m² plus immunomodulatory drugs and dexamethasone has shown efficacy and tolerability treating early relapsed/refractory multiple myeloma (RRMM). The phase 2 SELECT study (NCT04191616) evaluated efficacy/safety of weekly carfilzomib, pomalidomide, and dexamethasone (KPd) in early RRMM patients refractory to lenalidomide. All 52 treated patients were refractory to prior treatment, and 19 (37%) were triple-class refractory. Overall response rate (ORR; primary endpoint) was 58% (35% ≥ very good partial response, 6% ≥ complete response); median response duration was 20.3 months. Minimal residual disease negativity (10^-5) was achieved in 10% of patients. Median progression-free survival was 11.1 months; median overall survival was 18.8 months. Adverse events (AEs) were consistent with the known safety profile including grade ≥3 treatment-emergent AEs reported in 67% of patients. Although the primary endpoint of ORR was not met, KPd showed meaningful clinical benefits in lenalidomide-refractory RRMM patients, including those who were daratumumab-refractory and/or triple-class refractory.