Monday, July 1, 2019

FDA approval of daratumumab for Multiple Myeloma

The Food and Drug Administration (FDA) announced their approval of daratumumab in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant.

“Today’s approval of DARZALEX (daratumumab) underscores the significant clinical benefit of this CD38 monoclonal antibody and our efforts to advance treatment paradigms to change the course of the disease,” said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC in a press release. “Importantly, this milestone also highlights the efficiency of the FDA’s Real-Time Oncology Review process, ensuring that proven treatment regimens, such as DARZALEX plus lenalidomide and dexamethasone, are made available to patients as soon as possible.”
The decision for approval was made based on results of MAIA, an open-label, randomized (1:1) phase III study comparing dartumumab (16 mg/kg) in combination with lenalidomide and low-dose dexamethasone (DRd) to lenalidomide and low-dose dexamethasone (Rd), in 737 patients.
The trial showed an improvement in progression-free survival (PFS) with DRd compared with Rd. The median PFS had not been reached in the DRd arm and was 31.9 months in the Rd arm (HR 0.56; 95% CI: 0.43, 0.73; p<0.0001). The median time to response was 1.05 months (range: 0.2 to 12.1 months) in the DRd group and 1.05 months (range: 0.3 to 15.3 months) in the Rd group. The median response duration had not been reached in the DRd group and was 34.7 months (95% CI: 30.8, not estimable) in the Rd group.
In the DRd arm, the most frequent (≥20%) adverse reactions were infusion reactions, 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.
Daratumumab can cause severe and/or serious infusion reactions, including anaphylactic-related ones. Patients should be pre‑medicated with antihistamines, antipyretics and corticosteroids and frequently monitored during the entire infusion. The recommended daratumumab dose is 16 mg/kg actual body weight. 
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