Efficacy and Safety of Daratumumab, Pomalidomide and Dexamethasone Compared to Daratumumab, Carfilzomib and Dexamethasone in Relapsed Multiple Myeloma: Multicenter Real-World Experience

BACKGROUND: Daratumumab-based triplet regimens have demonstrated efficacy in relapsed or refractory multiple myeloma (RRMM). However, direct comparisons between these combinations remain limited. This study evaluated the efficacy and safety of 2 such regimens, DPd (daratumumab, pomalidomide, and dexamethasone) and DKd (daratumumab, carfilzomib, and dexamethasone), in a real-world RRMM population. METHODS: We conducted a multicenter retrospective cohort study including 399 patients with RRMM treated at three academic centers in the US. The patients received either DPd (n = 295) or DKd (n = 104). Progression-free survival (PFS), overall survival (OS), depth of response, and adverse event profiles were compared between the groups. RESULTS: The median PFS was 15 and 12 months in the DPd and DKd groups, respectively. The median OS was 38 months for DPd and was not reached in the DKd cohort. The differences in PFS (P = .2) and OS (P = .5) were not statistically significant. The overall response rates and depth of response were comparable across regimens. DPd was associated with higher rates of hematologic toxicity, particularly grade ≥ 3 neutropenia (36% vs. 23%) and leukopenia (26% vs. 14%), whereas DKd showed a greater incidence of cardiovascular adverse events (29% vs. 18%). CONCLUSIONS: DPd and DKd demonstrated similar clinical efficacies in RRMM patients, although their toxicity profiles differed. These findings highlight the importance of individualized treatment decisions considering underlying patient comorbidities and prior drug exposure. These findings support the use of either regimen in appropriate patient subsets, based on efficacy and distinct safety profiles.