On June 27, 2019, the FDA approved daratumumab (Darzalex; Janssen) in combination with lenalidomide (Revlimid; Celgene) and dexamethasone for the first-line treatment of patients with multiple myeloma who are ineligible for autologous stem-cell transplantation (ASCT). This approval was granted a priority review and used the Oncology Center of Excellence Real-Time Oncology Review program. This is the sixth indication for daratumumab in multiple myeloma and the second indication for newly diagnosed patients.
This latest approval was based on results of the randomized, open-label, multicenter phase 3 MAIA clinical trial of 737 patients with newly diagnosed multiple myeloma who were not candidates for high-dose chemotherapy and ASCT. The patients were randomized in a 1:1 ratio to daratumumab plus lenalidomide and dexamethasone or to lenalidomide and dexamethasone alone.
The addition of daratumumab showed improvement in progression-free survival (PFS). The median PFS had not been reached in the daratumumab arm versus 31.9 months in the lenalidomide plus dexamethasone arm (hazard ratio, 0.56; 95% confidence interval, 0.43-0.73; P <.0001). The addition of daratumumab also resulted in higher rates of complete response or better than with lenalidomide and dexamethasone alone (48% vs 25%, respectively) and overall response (93% vs 81%, respectively), as well as a higher rate of minimal residual disease negativity (24% vs 7%, respectively).
The most frequent (≥20%) adverse events associated with daratumumab-based therapy were infusion reactions, diarrhea, constipation, nausea, peripheral edema, fatigue, back pain, asthenia, pyrexia, upper respiratory tract infection, bronchitis, pneumonia, decreased appetite, muscle spasms, peripheral sensory neuropathy, dyspnea, and cough.