Early versus late response to daratumumab-based triplet therapies in patients with multiple myeloma: a pooled analysis of trials POLLUX, CASTOR and MAIA

Abstract

In multiple myeloma (MM), it is unclear whether early and late responders to daratumumab have similar outcomes. We pooled individual-level data from phase 3 trials and divided them into early and late response groups based on median time to response. Altogether 670 and 213 patients achieved very good partial response (VGPR) or better and minimal residual disease (MRD) negativity, respectively. Among VGPR or better, there was no significant difference of modified progression-free survival (mPFS, hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.69-1.44) or duration of response (DOR) (HR 1.02, 95%CI 0.68-1.53). Among relapsed/refractory MM (RRMM) achieving MRD negativity, late responders had significantly longer mPFS (p = 0.038) and DOR (p = 0.043). These results support that for patients who failed to achieve an early response to daratumumab, therapies should be continued with the goal of achieving ongoing and stepwise improvement of response.

Keywords: Multiple myeloma; daratumumab; minimal residual disease; response kinetics.