Research presented at the European Hematology Association 24th Congress found that the addition of daratumumab to bortezomib, thalidomide, and dexamethasone significantly improved responses without impacting safety in patients with newly diagnosed multiple myeloma (MM) who are eligible for autologous hematopoietic cell transplantation. The results of the study were also published in The Lancet.
The two-part, randomized, open-label, phase III CASSIOPEIA trial recruited 1,085 transplant-eligible patients with newly diagnosed MM from 111 European sites between September 22, 2015, and August 1, 2017. Patients were randomized 1:1 to receive four pre-transplant induction and two post-transplant consolidation cycles of bortezomib, thalidomide, and dexamethasone alone (VTd; n=542) or VTd in combination with daratumumab (D-VTd; n=543).
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Improved response with addition of daratumumab
At 100 days post-transplantation, 157 patients (29%) in the D-VTd group and 110 (20%) in the VTd group achieved a stringent complete response (CR; odds ratio = 1.60; 95% CI, 1.21-2.12; P=0.0010). In the D-VTd group, 211 patients (39%) achieved a CR or better, while 141 (26%) in the VTd group did so. Minimal residual disease negativity was reached in 346 patients (64%) in the D-VTd group and 236 (44%) of the VTd group (P<0.0001 for both).
After a median follow-up of 18.8 months, median progression-free survival (PFS) was not reached in either group, but the rate of PFS favored D-VTd (92.7% vs. 84.6%; hazard ratio = 0.47; 95% CI, 0.33-0.67; P<0.0001), representing a 53% reduced risk of progression or death with the addition of daratumumab. Median overall survival (OS) was not reached in either cohort, but the 24-month OS rate in the D-VTd group was 97%.
A total of 46 deaths occurred: 14 in the D-VTd group and 32 in the VTd group. The most common grade 3/4 adverse events were neutropenia (28% vs. 15%), lymphopenia (17% vs. 10%), and stomatitis (13% vs. 16%).