Daratumumab demonstrated superior efficacy in combination with lenalidomide and dexamethasone (DRd) compared with lenalidomide and dexamethasone alone (Rd) in a prespecified interim analysis of a randomized phase 3 study of relapsed or refractory multiple myeloma. In this updated analysis of the POLLUX study, Usmani and colleagues reported subgroup analyses of this study in patients who received 1 to 3 prior lines of therapy, including outcomes based on high-risk cytogenetics.
Patients who received ≥1 prior lines of therapy were randomized to Rd with or without daratumumab. Patients with high-risk cytogenetic status had at least 1 of the following abnormalities: t(4;14), t(14;16), or del17p.
There were 286 and 283 patients in the DRd and Rd arms, respectively. Median age was 65 in both arms; other clinical characteristics were similar. In the updated efficacy analysis, at 18 months of follow-up, the median progression-free survival (PFS) was superior in the group randomized to DRd, whose median PFS had not yet been reached (NR), compared with 17.5 months for the patients randomized to Rd (hazard ratio [HR], 0.37; P<0.0001). The estimated 18-month PFS rates were 76% and 49%, respectively. In patients with high-risk cytogenetics, in this subgroup, median PFS was not reached in the DRd group compared with 10.2 months in the Rd group (HR, 0.44; P=0.0475). Among patients who received 1 to 3 prior lines of therapy who were refractory to their last line of therapy, median PFS was significantly prolonged at 18 months with DRd versus Rd (NR vs 10.3 months; HR, 0.47; P=0.0015). Furthermore, data indicate that responses are deepening over time for patients receiving DRd. At 18 months, 87% showed an overall response ratio in the DRd arm compared with 64% in the Rd arm; nearly one-third (31.5%) were stringent complete responses.
Patients treated with DRd also showed better minimal residual disease (MRD)-negativity rates compared with those treated with Rd. At a sensitivity threshold of 10-4, 31.6% versus 8.8% of patients achieved MRD-negativity with DRd versus Rd. Likewise, at 10-5 and 10-6, 24.8% versus 5.7% and 11.9% versus 2.5% achieved MRD-negativity with DRd versus Rd, respectively.
The investigators concluded that the deep and durable responses associated with DRd translated into significantly improved clinical outcomes in patients who received 1 to 3 prior lines of therapy.
Usmani S, et al. ASH 2016. Abstract 1151.
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