Daratumumab is a human, CD38-targeting monoclonal antibody that has proven safety and efficacy in patients with relapsed/refractory multiple myeloma (RRMM). The CASTOR study is a multicenter, randomized phase 3 study of daratumumab, bortezomib, and dexamethasone (DVd) versus bortezomib and dexamethasone (Vd) in patients with RRMM.
For study inclusion, patients had received ≥1 prior lines of therapy; bortezomib-refractory patients were ineligible for study inclusion. Patients were administered either intravenous daratumumab 16 mg/kg once weekly in cycles 1 to 3, every 3 weeks for cycles 4 to 8, and then every 4 weeks until disease progression; bortezomib 1.3 mg/m2, 8 cycles every 3 weeks on days 1, 4, 8, and 11; and dexamethasone 20 mg on days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 in the DVd group, or just bortezomib and dexamethasone in the Vd group. Minimal residual disease (MRD) was assessed upon suspected complete response (CR), and at 6 and 12 months following the first dose. The median age of patients was 64 years, and patients received a median of 2 (range, 1-10) prior lines of therapy. After a median study follow-up of 19.4 months, progression-free survival (PFS) was prolonged significantly with DVd (16.7 months) versus Vd (7.1 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.24-0.39; P <0.0001). The benefit observed in PFS was seen regardless of the number of prior therapies patients received, with the greatest benefit observed in patients who had received 1 prior line of therapy (median: not reached vs 7.9 months; HR, 0.22; 95% CI, 0.14-0.34; P <0.0001). Overall response rate was also significantly higher for patients receiving DVd versus Vd (84% vs 63%). Sixty-two percent of patients in the DVd group reported ≥very good partial response versus 29% of patients in the Vd group (P <0.0001), and a significant difference in ≥CR was seen in patients in the DVd group, as well (29% vs 10%, respectively; P <0.0001). MRD-negativity rates were more than 3-fold higher with patients receiving DVd versus Vd. Patients who achieved MRD negativity demonstrated prolonged PFS compared with MRD-positive patients.
The most common grade 3/4 treatment-emergent adverse event reported was thrombocytopenia in 46% of DVd patients versus 33% of Vd patients. Median overall survival has not been reached for either group; however, to date, deaths have been reported in 59 (23.5%) and 75 (30.4%) patients receiving DVd and Vd, respectively, and the study follow-up is ongoing.
This study demonstrated that DVd provided sustained efficacy versus Vd. No new safety or tolerability signals were reported in this study. These data continue to support the use of DVd in patients with RRMM, and indicate that patients with 1 prior line of therapy will derive the most benefit.
Lentzsch S, et al. ASCO Abstract 8036.
