On November 21, 2016, the U.S. Food and Drug Administration (FDA) approved daratumumab (Darzalex) in combination with lenalidomide (Revlimid) and dexamethasone or bortezomib (Velcade) and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.1
Daratumumab is a CD38-directed cytolytic antibody and was previously granted accelerated approval in November 2015 as monotherapy for patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double refractory to a proteasome inhibitor and an immunomodulatory agent.
Pivotal Trials
The current approval was based on two randomized, open-label trials in which daratumumab was added to standard therapies. The POLLUX trial demonstrated substantial improvement in progression-free survival when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone.2 The estimated median progression-free survival had not been reached in the daratumumab arm and was 18.4 months in the control arm (HR = 0.37; 95% confidence interval [CI] = 0.27–0.52; P < .0001), representing a 63% reduction in the risk of disease progression or death in patients treated with daratumumab.
Similar results were observed in the CASTOR trial, which compared the combination of daratumumab, bortezomib, and dexamethasone with bortezomib and dexamethasone.3 The estimated median progression free survival was not reached in the daratumumab arm and was 7.2 months in the control arm (HR = 0.39; 95% CI = 0.28–0.53; P < .0001), representing a 61% reduction in the risk of disease progression or death for patients treated with daratumumab.
Adverse Events
The most frequently reported adverse reactions (greater than or equal to 20%) were infusion reactions, neutropenia, thrombocytopenia, fatigue, nausea, diarrhea, muscle spasms, back pain, pyrexia, cough, dyspnea, peripheral edema, peripheral sensory neuropathy, and upper respiratory tract infection.
The recommended dose of daratumumab is 16 mg/kg intravenously (calculated on actual body weight).
For more on daratumumab in this issue of The ASCO Post, see pages 26 and 27. Plus watch future issues of The ASCO Post for reports on the two pivotal studies as published in The New England Journal of Medicine. ■
References
1. U.S. Food and Drug Administration: Daratumumab (Darzalex). Available at www.fda.gov/Drugs/InformatinOnDrugs/ApprovedDrugs/ucm530249.htm. Accessed November 29, 2016.
