As reported in The Lancet Oncology by Thierry Facon, MD, and colleagues, an interim analysis of overall survival in the pivotal phase III MAIA trial has shown a significant benefit with the addition of daratumumab to lenalidomide/dexamethasone in newly diagnosed, transplant-ineligible patients with multiple myeloma.

The primary analysis of the trial supported the June 2019 approval of daratumumab in combination with lenalidomide and dexamethasone in this setting, showing superior progression-free survival with the regimen after a median follow-up of 28.0 months.

Thierry Facon, MD

Study Details

The open-label trial included 737 transplant-ineligible patients from sites in 14 countries who were randomly assigned to one of two treatment groups between March 2015 and January 2017. Patients either received 28-day cycles of daratumumab (16 mg/kg once per week during cycles 1 and 2, once every 2 weeks in cycles 3 to 6, and once every 4 weeks thereafter) plus lenalidomide (25 mg on days 1 to 21 of each cycle) and oral dexamethasone (40 mg on days 1, 8, 15, and 22 of each cycle; daratumumab group, n = 368) or lenalidomide/dexamethasone alone (control group, n = 369).

Treatment was continued until disease progression or unacceptable toxicity. Overall survival was a secondary endpoint.

Overall Survival and Updated Efficacy Results

Median follow-up was 56.2 months (interquartile range = 52.7–59.9 months) at time of interim analysis. With prolonged follow-up, median progression-free survival was not reached (95% confidence interval [CI] = 54.8 months–not reached) in the daratumumab group vs 34.4 months (95% CI = 29.6–39.2 months) in the control group (hazard ratio [HR] = 0.53, 95% CI = 0.43–0.66, P < .0001); estimated progression-free survival at 60 months was 52.5% (95% CI = 46.7%–58.0%) vs 28.7% (95% CI = 23.1%≠34.6%). Median time to disease progression was not reached (95% CI = not reached–not reached) vs 40.9 months (95% CI = 35.8–49.2 months).

Subsequent therapy was received by 31% of the daratumumab group and 51% of the control group at clinical cutoff. By that time, death had occurred in 32% of patients in the daratumumab group and 42% of those in the control group.

Median overall survival was not reached (95% CI = not reached–not reached) in the daratumumab group vs not reached (95% CI = 55.7 months–not reached) in the control group (HR = 0.68, 95% CI = 0.53–0.86, P = .0013). Estimated 60-month overall survival was 66.3% (95% CI = 60.8%–71.3%) in the daratumumab group vs 53.1% (95% CI = 47.2%–58.6%) in the control group.

Updated overall response rates were 92.9% vs 81.6% (odds ratio [OR] = 3.00, P< .0001), with complete response or better in 51% vs 30% (OR = 2.44, P < .001). Measurable residual disease–negative status was achieved in 31% vs 10% (OR = 3.91, P < .0001).

Adverse Events

The most common (> 15% in either group) grade ≥ 3 adverse events were neutropenia (54% of the daratumumab group vs 37% of the control group), pneumonia (19% vs 11%), anemia (17% vs 22%), and lymphopenia (16% vs 11%). Grade ≥ 3 infections occurred in 41% vs 29% of patients.

Serious adverse events occurred in 77% vs 70%, with the most common being pneumonia (18% vs 11%). Second primary malignancies were reported in 20% vs 13% of patients. Treatment-related death occurred in 4% vs 3% of patients.

The investigators concluded, “Daratumumab plus lenalidomide and dexamethasone increased overall survival and progression-free survival in patients ineligible for stem cell transplantation with newly diagnosed multiple myeloma. There were no new safety concerns. Our results support the front-line use of daratumumab plus lenalidomide and dexamethasone for patients with multiple myeloma who are ineligible for transplantation.”

Dr. Facon, of the University of Lille, Centre Hospitalier Universitaire de Lille, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Janssen Research & Development. For full disclosures of the study authors, visit thelancet.com.