The Food and Drug Administration has granted accelerated approval to daratumumab for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, the agency announced Nov. 16. Daratumumab is the first monoclonal antibody approved for the treatment of multiple myeloma.
Approval was based on an objective response rate of 29% (95% confidence interval, 21%-39%) with a median response duration of 7.4 months in 106 patients with relapsed or refractory multiple myeloma treated with daratumumab monotherapy in a multicenter, open-label study.
Safety was evaluated in 156 patients in two open-label studies. The most frequently reported adverse reactions were infusion reactions, fatigue, nausea, back pain, pyrexia, cough, and upper respiratory tract infection. The most common laboratory abnormalities were lymphopenia, neutropenia, anemia, and thrombocytopenia, the FDA said.
Daratumumab, marketed as Darzalex, interferes with blood bank cross-matching, specifically with Indirect Antiglobulin Tests, and the FDA recommends that, if a transfusion is necessary, to inform the blood bank that a patient has received daratumumab.
As a condition of accelerated approval, the FDA is requiring manufacturer Janssen Biotech to follow-up with a randomized trial establishing the superiority of daratumumab over standard therapy. The company has several ongoing multicenter, randomized trials in patients with multiple myeloma with a primary endpoint of progression-free survival.
The recommended dose and schedule for daratumumab is 16 mg/kg once every week for 8 weeks, then once every 2 weeks for 16 weeks, then once every 4 weeks until disease progression.