Daratumumab demonstrated superior efficacy when combined with lenalidomide plus dexamethasone compared with lenalidomide and dexamethasone alone in a prespecified interim analysis of a randomized phase 3 clinical trial of patients with relapsed or refractory multiple myeloma. In the subgroup analyses of the POLLUX study, Usmani and colleagues evaluated outcomes in patients who received 1 to 3 previous lines of therapy, including outcomes based on high-risk cytogenetic therapy.
The patients were randomized to receive lenalidomide and dexamethasone with daratumumab (N = 286) or without daratumumab (N = 283). Patients with high-risk cytogenetic status had ≥1 abnormalities, including t(4;14), t(14;16), or del17p. The median age was 65 years in both arms, and other clinical characteristics were similar.
At 18 months of follow-up, the median progression-free survival (PFS) was not reached in the group that received the combination with daratumumab compared with 17.5 months in the group that received lenalidomide and dexamethasone alone (P <.0001). The estimated 18-month PFS rates were 76% and 49%, respectively.
In the subgroup of patients with high-risk cytogenetics, median PFS was not reached with the 3-drug combination arm versus 10.2 months with lenalidomide and dexamethasone alone (P = .475). Among patients who received 1 to 3 previous lines of therapy whose disease was refractory to the last line of therapy, the median PFS at 18 months was significantly prolonged with the 3-drug regimen versus the 2-drug regimen with lenalidomide and dexamethasone (not reached vs 10.3 months). Furthermore, the data showed that responses deepened over time for patients receiving the 3-drug regimen. At 18 months, the overall response rate was 87% in the 3-drug combination arm versus 64% in the 2-drug arm; approximately 31.5% of these were stringent complete responses.
Patients who received the daratumumab combination therapy also showed better minimal residual disease (MRD)-negativity rates compared with those receiving lenalidomide and dexamethasone alone. At a sensitivity threshold of 10-4, 31.6% versus 8.8% of patients achieved MRD-negativity with daratumumab combination therapy versus lenalidomide and dexamethasone alone, respectively.
The investigators concluded that the deep and durable responses associated with daratumumab when added to lenalidomide and dexamethasone translated into significantly improved clinical outcomes in this patient population.