Until recently, patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation (ASCT), the multiagent regimen with lenalidomide (Revlimid) and dexamethasone was the standard of care. Results of the prespecified interim analysis of the MAIA trial demonstrated the benefit of adding daratumumab (Darzalex) to this combination therapy (Facon T, et al. N Engl J Med. 2019;380:2104-2115). Based on the results of this study, on July 1, 2019, the FDA approved this triple-drug regimen for use in this patient population.
MAIA was a randomized, open-label, international, phase 3 clinical trial of 737 adults with newly diagnosed multiple myeloma who were ineligible for ASCT. The patients were randomized in a 1:1 ratio to daratumumab, lenalidomide, and dexamethasone, or to standard of care with lenalidomide plus dexamethasone alone (control group). During the 28-day cycle, all patients received oral lenalidomide 25 mg on days 1 through 21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the 3-drug arm also received intravenous daratumumab 16 mg/kg once weekly for cycles 1 and 2, every 2 weeks for cycles 3 through 6, and then every 4 weeks thereafter. Treatment was continued until disease progression or unacceptable toxicities. The primary end point was progression-free survival (PFS). The secondary end points were time to disease progression, complete response (CR), and overall survival.
After a median follow-up of 28 months, disease progression or death had occurred in 26.4% of the patients in the daratumumab arm compared with 38.8% in the control group. The median PFS was not reached in the daratumumab arm and was 31.9 months in the control group. Overall, a 44% lower risk for disease progression or death was observed among the daratumumab cohort than in the control group (hazard ratio, 0.56).
The benefit of adding daratumumab was also seen in CR and minimal residual disease (MRD). The percentage of patients with a CR or better was nearly 2 times higher in the daratumumab arm than in the control group (47.6% vs 24.9%, respectively); the percentage of patients who had negative MRD was more than 3 times higher in the daratumumab group than in the control group (24.2% vs 7.3%, respectively).
As expected, certain adverse events were higher with the 3-drug regimen than the 2-drug regimen. Grade 3 or 4 neutropenia was 50% in the daratumumab arm versus 35.3% in the control group; lymphopenia rates were 15.1% versus 10.7%, respectively; pneumonia, 13.7% versus 7.9%, respectively; and leukopenia, 11% versus 4.9%, respectively. Overall, the rates of serious adverse events, including those that resulted in death, were similar in the 2 groups.
“These findings can be added to those from a growing list of trials that support the use of daratumumab-based regimens across patient populations with multiple myeloma,” the researchers observed. With the recent FDA approval of this 3-drug regimen, adding daratumumab to lenalidomide and dexamethasone will likely become the new standard of care in newly diagnosed patients who are ineligible for ASCT.