On September 26, 2019, the U.S. Food and Drug Administration approved daratumumab (Darzalex) in combination with bortezomib, thalidomide, and dexamethasone for newly diagnosed adult patients with multiple myeloma who are eligible for autologous stem cell transplant (ASCT).
Efficacy was investigated in the CASSIOPEIA trial, an open-label, randomized, active-controlled phase III study comparing induction and consolidation treatment with daratumumab 16 mg/kg in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) to treatment with bortezomib, thalidomide, and dexamethasone (VTd) in patients with newly diagnosed multiple myeloma eligible for ASCT. The FDA had previously granted this application priority review.
Approval is based on data from CASSIOPEIA, including progression-free survival (PFS), stringent complete response at 100 days post-ASCT, and CR rate at day 100 post-ASCT. The trial demonstrated an improvement in PFS in the D-VTd arm as compared to the VTd arm; with a median follow up of 18.8 months, the median PFS had not been reached in either arm. Treatment with D-VTd resulted in a reduction in the risk of progression or death by 53% compared to VTd alone (hazard ratio [HR] = 0.47; 95% confidence interval [CI] = 0.33–0.67; P < .0001). The stringent complete response rate at day 100 post-ASCT was 28.9% in the D-VTd arm and 20.3% in the VTd arm.
In patients with newly diagnosed multiple myeloma who received daratumumab in combination with bortezomib, thalidomide, and dexamethasone, the most frequent (≥ 20%) adverse reactions were infusion reactions, peripheral sensory neuropathy, constipation, asthenia, nausea, peripheral edema, neutropenia, thrombocytopenia, pyrexia, and paresthesia. Adverse reactions that occurred with at least 5% greater frequency in the D-VTd arm were infusion reactions, nausea, neutropenia, thrombocytopenia, lymphopenia, and cough. There were no significant differences in the number or type of serious adverse events in the two treatment arms.
The recommended daratumumab dose is 16 mg/kg actual body weight.