The U.S. Food and Drug Administration (FDA) has approved the use of the monoclonal antibody daratumumab (Darzalex) in combination with pomalidomide (Pomalyst) and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies including lenalidomide (Revlimid) and a proteasome inhibitor.
The approval was based on data from the phase I (MMY1001, EQUULEUS) study of daratumumab in combination with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma. Daratumumab targets the CD38 protein.
About the Study
One arm of the phase I EQUULEUS open-label study included 103 patients with multiple myeloma who had received prior treatment with a proteasome inhibitor and an immunomodulatory agent. Patients in the study received 16 mg/kg of daratumumab in combination with pomalidomide and -dexamethasone.
The overall response rate in the study was 59% (95% confidence interval [CI] = 49.1%–68.8%), with a very good partial response achieved in 28% of patients. Complete response was achieved in 6% of patients, and stringent complete response was achieved in 8% of patients. The median time to response was 1 month (range = 0.9–2.8 months). The median duration of response was 13.6 months (range = 0.9+ to 14.6+ months).
The most frequent adverse reactions (> 20%) in the study were infusion reactions, diarrhea, nausea, vomiting, fatigue, pyrexia, upper respiratory tract infection, muscle spasms, cough, and dyspnea. The overall incidence of serious adverse reactions was 49%.Serious adverse reactions (grade 3/4) reported in ≥ 5% patients included pneumonia.
Prior Approval
Daratumumab was approved previously for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone, in people who have received at least one prior medicine to treat multiple myeloma and alone in people who have received at least three prior medicines to treat multiple myeloma, including a proteasome inhibitor and an immunomodulatory agent, or did not respond to a proteasome inhibitor and an immunomodulatory agent. ■
