Daratumumab is a human CD38-targeting monoclonal antibody that provides significantly prolonged progression-free survival (PFS) when added to standard-of-care regimens in patients with relapsed/refractory multiple myeloma (RRMM). POLLUX is a randomized phase 3 study of daratumumab, lenalidomide, and dexamethasone (DRd) versus lenalidomide and dexamethasone (Rd) in patients with RRMM; researchers provided an update on the safety and efficacy data from this trial.
In this study, patients with ≥1 prior lines of therapy received either intravenous daratumumab 16 mg/kg every week for cycles 1 and 2, every 2 weeks for cycles 3 to 6, and then every 4 weeks thereafter, in combination with lenalidomide 25 mg on days 1 to 21 of every 4-week cycle, and dexamethasone 40 mg once per week (DRd), or lenalidomide and dexamethasone (Rd). Patients were excluded from the study if they were refractory to lenalidomide therapy. Minimal residual disease (MRD) was assessed on bone marrow samples at the time of suspected complete response (CR), and at 3 and 6 months after suspected CR. Patient characteristics were well-balanced between the DRd and Rd arms of the study. Patients received a median of 1 (range, 1-11) prior line of therapy, and 55% of patients had received prior immunomodulatory drugs (18% lenalidomide).
At a median follow-up of 25.4 months, DRd significantly prolonged PFS compared with Rd, with a median PFS not reached versus 17.5 months in patients in the Rd group (hazard ratio, 0.41; 95% confidence interval, 0.31-0.53; P <0.0001). Overall response rates (ORRs) were also significantly improved in the DRd group versus the Rd group, at 93% compared with 76%, respectively (P <0.0001). Patients in the DRd group reported significantly higher CR rates versus Rd (51% vs 31%; P <0.0001). MRD negativity was more than 3-fold higher for DRd versus Rd, and MRD-negative patients demonstrated longer PFS versus MRD-positive patients. At data cutoff, overall survival was not reached in either arm but follow-up is ongoing. Thus far, 63 deaths have been reported in the DRd arm, compared with 79 deaths in the Rd arm. No new safety or tolerability signals were identified in this study.
DRd provided significant ORR and PFS benefits versus Rd, induces deep and durable responses, and induces more rapid accumulation of MRD negativity compared with Rd. These data further validate the clinical utility of DRd in patients with RRMM.
Bahlis NJ, et al. ASCO Abstract 8025.
