In the phase III MAIA trial reported in The New England Journal of Medicine, Facon et al found that the addition of daratumumab to lenalidomide/dexamethasone significantly improved progression-free survival in previously untreated multiple myeloma ineligible for autologous stem cell transplantation (ASCT).
The open-label trial included 737 patients from 176 sites in 14 countries. Patients were randomly assigned between March 2015 and January 2017 to receive daratumumab plus lenalidomide/dexamethasone (n =368) or lenalidomide/dexamethasone alone (n = 369). All patients received 28-day cycles of lenalidomide at 25 mg on days 1 through 21 and dexamethasone at 40 mg on days 1, 8, 15, and 22 until disease progression or unacceptable toxicity. Daratumumab was given at 16 mg/kg once weekly during cycles 1 and 2, every 2 weeks during cycles 3 through 6, and every 4 weeks thereafter.
The primary endpoint was progression-free survival. At a median follow-up of 28.0 months, progression-free survival events had occurred in 26.4% of patients in the daratumumab group and 38.8% of patients in the control group. The estimated 30-month progression-free survival was 70.6% vs 55.6% (hazard ratio = 0.56, P < .001).
A complete response or better was achieved in 47.6% vs 24.9% of patients (P < .001). Responses below the threshold for minimal residual disease (1 tumor cell per 105 white cells) were achieved in 24.2% vs 7.3% of patients (P < .001). At the time of analysis, death had occurred in 16.8% of the daratumumab group and 20.6% of the control group. Follow-up for long-term survival is ongoing.
The most common grade 3 or 4 adverse events were neutropenia (50.0% in the daratumumab group vs 35.3% in the control group), anemia (11.8% vs 19.7%), lymphopenia (15.1% vs 10.7%), and pneumonia (13.7% vs 7.9%). Grade 3 or 4 infections occurred in 32.1% vs 23.3% of patients. Serious adverse events occurred in 62.9% vs 62.7% of patients, with the most common being pneumonia (13.2% vs 7.4%).
The investigators concluded, “Among patients with newly diagnosed multiple myeloma who were ineligible for ASCT, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among those who received lenalidomide and dexamethasone alone. A higher incidence of neutropenia and pneumonia was observed in the daratumumab group.”
Disclosure: The study was funded by Janssen Research and Development. For full disclosures of the study authors, visit nejm.org.
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