The FDA has now approved daratumumab (Darzalex®, Janssen Biotech, Inc.) in combination with lenalidomide and dexamethasone as a first-line treatment for patients with multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).
The approval was based on MAIA (NCT02252172), an open-label, active-controlled phase 3 trial that randomized 737 ASCT-ineligible patients with newly diagnosed multiple myeloma to receive either daratumumab plus lenalidomide/dexamethasone or lenalidomide/dexamethasone alone.
"Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation," wrote the authors of the study, led by Thierry Facon, MD, Professor of Hematology at Lille University Hospital, Lille, France, in their publication in The New England Journal of Medicine. "We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population."
At a median follow-up of 28.0 months, 26.4% of patients in the daratumumab group had experienced disease progression or death, compared with 38.8% of patients receiving lenalidomide/dexamethasone alone. More patients in the daratumumab group were alive without disease progression at 30 months (70.6% vs 55.6%). Daratumumab produced a higher complete response rate (47.6% vs 24.9%) and increased the rate of patients achieving minimal residual disease (24.2% vs 7.3%).
The recommended dose of daratumumab is 16 mg/kg. In the phase 3 trial, the most common grade 3/4 adverse events included neutropenia (50.0% in the daratumumab group vs 35.3% in the lenalidomide/dexamethasone-only group), anemia (11.8% vs 19.7%), lymphopenia (15.1% vs 10.7%), and pneumonia (13.7% vs 7.9%). In patients receiving daratumumab/lenalidomide/dexamethasone, adverse reactions of any grade occurring in at least 20% of patients included 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.
For More Information
Clinicaltrials.gov (2019). Study comparing daratumumab, lenalidomide, and dexamethasone with lenalidomide and dexamethasone in participants with previously untreated multiple myeloma. NLM identifier: NCT02252172.
Image credit: KGH. Licensed under CC BY-SA 3.0