FDA Approves Daratumumab in Combination With Lenalidomide/Dexamethasone or Bortezomib/Dexamethasone in Multiple Myeloma
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.
Daratumumab 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 (PI) and an immunomodulatory agent, or who are double refractory to a PI and an immunomodulatory agent.
POLLUX
The current approval was based on two randomized, open-label trials in which daratumumab was added to standard therapies. The POLLUX trial (also known as MMY3003), demonstrated substantial improvement in progression-free survival when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone. The estimated median progression-free survival had not been reached in the daratumumab arm and was 18.4 months in the control arm (hazard ratio [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.
CASTOR
Similar results were observed in the CASTOR trial (also known as MMY3004), which compared the combination of daratumumab, bortezomib, and dexamethasone with bortezomib and dexamethasone. 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.
The most frequently reported adverse reactions (≥ 20%) in MMY3003 were infusion reactions, diarrhea, nausea, fatigue, pyrexia, upper respiratory tract infection, muscle spasm, cough, and dyspnea. The most frequently reported adverse reactions (≥ 20%) in MMY3004 were infusion reactions, diarrhea, peripheral edema, upper respiratory tract infection, peripheral sensory neutropenia, and thrombocytopenia.
The recommended dose of daratumumab is 16 mg/kg intravenously (calculated on actual body weight).
FDA granted daratumumab breakthrough therapy and orphan drug designation, as well as priority review. The current approval was granted 3 months prior to the PDUFA date of February 17, 2017. Full prescribing information is available here.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
