FDA Approves Daratumumab in Combination With Lenalidomide and Dexamethasone for Newly Diagnosed Multiple Myeloma

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On June 27, the U.S. Food and Drug Administration (FDA) approved daratumumab (Darzalex) in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). The application received approval through the FDA’s Real-Time Oncology Review pilot program.

The approval is based on results from the phase III MAIA clinical trial, which showed that the addition of daratumumab to lenalidomide/dexamethasone significantly reduced the risk of disease progression or death by 44% compared with treatment with lenalidomide/dexamethasone alone. Data from the MAIA study were recently published in The New England Journal of Medicine1 and were presented by Facon et al at the 2018 American Society of Hematology Annual Meeting.2

More About MAIA

The randomized, open-label, multicenter phase III study included 737 newly diagnosed patients with multiple myeloma who are ineligible for high-dose chemotherapy and ASCT between the ages of 45 and 90. Patients were randomly assigned to receive either daratumumab plus lenalidomide/dexamethasone or lenalidomide/dexamethasone alone in 28-day cycles. In those treated with daratumumab plus lenalidomide/dexamethasone, the dose was 16 mg/kg of intravenous daratumumab weekly for cycles 1 to 2, every 2 weeks for cycles 3 to 6, and every 4 weeks for cycle 7 and thereafter. Those treated with daratumumab plus lenalidomide/dexamethasone and those treated with lenalidomide/dexamethasone received 25 mg of lenalidomide on days 1 to 21 of each 28-day cycle and dexamethasone at 40 mg once a week for each cycle. Patients in both treatment arms continued treatment until disease progression or unacceptable toxicity.

Results and Toxicity

At a median follow-up of 28 months, the results showed daratumumab plus lenalidomide/dexamethasone significantly reduced the risk of disease progression or death by 44% in patients with newly diagnosed multiple myeloma who are transplant-ineligible compared with treatment with lenalidomide/dexamethasone alone (hazard ratio [HR] = 0.56, 95% confidence interval [CI] = 0.43–0.73; P < .0001). The median progression-free survival for daratumumab plus lenalidomide/dexamethasone has not yet been reached, compared with 31.9 months for patients who received lenalidomide/dexamethasone alone. The addition of daratumumab resulted in deeper responses than lenalidomide/dexamethasone alone, including increased rates of complete response or better (48% vs 25%), very good partial response or better (79% vs 53%), and overall response (93% vs 81%). Daratumumab plus lenalidomide/dexamethasone induced a more than threefold higher rate of minimal residual disease negativity compared with lenalidomide/dexamethasone alone (24% vs 7%).

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. Serious adverse reactions with a 2% greater incidence in the daratumumab plus lenalidomide/dexamethasone arm compared with the lenalidomide/dexamethasone arm were pneumonia (15% vs 8%), bronchitis (4% vs 2%), and dehydration (2% vs < 1%). Treatment-emergent grade 3 or 4 hematology laboratory abnormalities (≥ 20%) were neutropenia (56%), lymphopenia (52%), and leukopenia (35%). The safety profile of daratumumab was consistent with that of previous studies. 


1. Facon T, Kumar S, Plesner T, et al: Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med 380:2104-2115, 2019.

2. Facon T, Kumar S, Plesner T, et al: Phase 3 randomized study of daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma ineligible for transplant (MAIA). 2018 ASH Annual Meeting & Exposition. Abstract LBA-2. Presented December 4, 2018.