Daratumumab demonstrated significant activity in combination with bortezomib and dexamethasone (DVd) compared with bortezomib and dexamethasone alone (Vd) in patients with relapsed or refractory multiple myeloma in the randomized phase 3 study known as CASTOR.1
Mateos and colleagues reported subgroup analyses of CASTOR, according to the number of prior lines of therapy received, and outcomes based on cytogenetic status. Eligible patients received at least 1 prior line of therapy and were randomized to 8 cycles of Vd with or without daratumumab. For each cycle, subcutaneous bortezomib was administered on days 1, 4, 8, and 11, and oral dexamethasone was given on days 1, 2, 4, 5, 8, 9, 11, and 12.
High-risk cytogenetic status was defined as having at least 1 of the following abnormalities via karyotyping or fluorescence in-situ hybridization: del17p, t(4;14), or t(14;16). Minimal residual disease was evaluated on bone marrow aspirate samples.
Median follow-up was 13.0 months in the updated efficacy analysis. A total of 251 patients in the DVd group and 247 in the Vd group received 1 to 3 prior lines of therapy. Median age was 64; patients received 2 prior lines of therapy. In this subgroup, median progression-free survival (PFS) was significantly longer with DVd versus Vd. The median PFS was not reached in the DVd arm and was 7.1 months in the Vd arm (hazard ratio [HR], 0.33; P<0.0001). The 12-month PFS rates were 60% versus 22%, respectively. An additional 7% of patients receiving DVd achieved complete response with longer follow-up, indicating that responses with DVd were deepening over time. Overall responses rates were 91% for DVd and 74% for Rd in patients receiving 1 prior line of therapy; and 79% versus 58%, respectively, for patients receiving 2 or 3 lines of therapy.
Among the group with standard-risk cytogenetic status, who received 1 to 3 prior lines, PFS was not reached in patients receiving DVd versus 7.0 months with Vd (HR, 0.29; P<0.0001). PFS was also significantly longer in patients with high-risk cytogenetics who received DVd versus Vd (11.2 months vs 7.2 months; HR, 0.49; P=0.0167).
Minimal residual disease (MRD)-negativity rates for DVd were at least 3-fold higher than Vd across all thresholds. At the 10-5 threshold, 12.3% of patients with 1 prior line of therapy receiving DVd were MRD-negative compared with 2.7% of patients in the Vd arm.
The investigators concluded that the treatment benefit of DVd compared with Vd was maintained regardless of the number of previous lines of therapy. The treatment benefit of DVd versus Vd was also observed in patients with high-risk cytogenetics who received 1 to 3 prior lines.
Mateos M-V, et al. ASH 2016. Abstract 1150.
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