Adding the monoclonal antibody daratumumab to lenalidomide and dexamethasone significantly improved progression-free survival in patients with relapsed or refractory multiple myeloma, according to the results of the POLLUX trial published in the New England Journal of Medicine.
Patients assigned to the three-drug combination had a 12-month progression-free survival rate of 83.2% compared with 60.1% in patients assigned lenalidomide/dexamethasone alone.
“The treatment effect of daratumumab was consistent regardless of previous exposure to lenalidomide and across all subgroups, including patients 65 years of age or older, those with disease that was refractory to proteasome inhibitors or the most recent line of therapy, those with International Staging System stage III disease, and those with previous exposure to a proteasome inhibitor or immunomodulatory drug,” wrote researchers led by Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens, Greece.
This phase III trial included 569 patients with myeloma who had received one or more previous lines of therapy. Patients were randomly assigned to lenalidomide/dexamethasone with daratumumab (n = 286) or without (n = 283). The primary endpoint was progression-free survival.
At a median follow-up of 13.5 months, results showed that patients assigned to daratumumab had a 63% lower risk for disease progression or death compared with patients on lenalidomide/dexamethasone alone. Disease progression or death had occurred in 18.5% of the daratumumab group compared with 41% of the control group (hazard ratio [HR], 0.37 [95% CI, 0.27–0.52]; P < .001).
“Progression-free survival was significantly prolonged with the addition of daratumumab regardless of the number of previous lines of therapy,” the researchers wrote. “Progression-free survival was similarly prolonged in the daratumumab group among patients who had previous exposure to lenalidomide and those who had no previous exposure, as compared with the control group.”
In addition, daratumumab treatment resulted in a significantly higher rate of overall response compared with lenalidomide/dexamethasone alone (92.9% vs 76.4%; P < .001), with a significantly higher percentage of patients assigned daratumumab achieving complete response or better (43.1% vs 19.2%; P < .001).
The most common grade 3 or 4 adverse events were neutropenia (51.9% for daratumumab vs 37.0% for control), thrombocytopenia (12.7% vs 13.5%), and anemia (12.4% vs 19.6%). In addition, almost one-half (47.7%) of patients assigned daratumumab had infusion-related reactions.
“Daratumumab with lenalidomide and dexamethasone was associated with clinically manageable adverse events that were consistent with the known toxic effects of lenalidomide and dexamethasone and of daratumumab,” the researchers wrote. “Although higher rates of neutropenia and infusion-related reactions (primarily during the first infusion) were observed with this combination than with lenalidomide and dexamethasone alone, these events did not result in higher rates of treatment discontinuation or death.”
The US Food and Drug Administration approved daratumumab in November 2015 for the treatment of patients with multiple myeloma with three or more prior lines of therapy. It was the first monoclonal antibody approved for multiple myeloma.