On June 27, 2019, the U.S. Food and Drug Administration (FDA) approved daratumumab, in combination with lenalidomide and dexamethasone, for patients with newly diagnosed multiple myeloma who are ineligible for autologous hematopoietic cell transplantation (AHCT). Approval was based on the phase III MAIA study, an open-label, randomized, active-controlled study comparing daratumumab 16 mg/kg plus lenalidomide and low-dose dexamethasone (DRd) with lenalidomide and low-dose dexamethasone alone (Rd) in 737 patients.
Patients randomized to receive the daratumumab combination had a longer progression-free survival (PFS) than those who received Rd: The median PFS had not been reached in the DRd arm and was 31.9 months in the Rd arm (hazard ratio = 0.56; 95% CI 0.43-0.73; p<0.0001). The median time to response was similar in each group (1.05 months [range = 0.2-12.1 months] in the DRd group and 1.05 months [range = 0.3-15.3 months] in the Rd group).
Approximately half of daratumumab-treated patients experienced infusion-related reactions, including anaphylactic response, so the FDA recommends that patients receive pre-medication with antihistamines, antipyretics, and corticosteroids (already a standard practice for when daratumumab is used for relapsed/refractory myeloma) and close monitoring is required during infusions. The most frequent adverse events with the DRd combination (occurring in >20% of patients) were 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.
This application was approved with priority review under the FDA’s Real-Time Oncology Review program.