On September 26, 2019, the FDA approved daratumumab (Darzalex; Janssen) in combination with bortezomib, thalidomide, and dexamethasone for the treatment of newly diagnosed patients with multiple myeloma who are eligible for autologous stem-cell transplant (ASCT). The FDA granted this application priority review.
This approval was based on data from the open-label, randomized, phase 3 CASSIOPEIA clinical trial, which compared induction and consolidation treatment with daratumumab plus bortezomib, thalidomide, and dexamethasone (DVTd) versus bortezomib, thalidomide, and dexamethasone (VTd) in newly diagnosed patients with multiple myeloma who were candidates for ASCT.
Results showed that the addition of daratumumab to VTd led to a 53% reduction in the risk of progression or death compared with VTd alone (hazard ratio, 0.47; 95% confidence interval, 0.33-0.67; P <.0001). The stringent complete response rate 100 days post-ASCT was 28.9% in the DVTd arm versus 20.3% in the VTd arm. At a median follow-up of 18.8 months, the median progression-free survival had not been reached in either arm.
The most common (≥20%) adverse reactions in patients who received DVTd were infusion reactions, peripheral sensory neuropathy, constipation, asthenia, nausea, peripheral edema, neutropenia, thrombocytopenia, pyrexia, and paresthesia.
The recommended daratumumab dose is 16 mg/kg of actual body weight.