The immunotherapy daratumumab (Darzalex) in combination with the standard-of-care regimen (lenalidomide plus dexamethasone) reduced risk of disease progression or death by 63% compared with the standard-of-care regimen alone in patients with multiple myeloma who had received at least 1 prior line of therapy (hazard ratio [HR] = 0.37; 95% CI, 0.27-0.52; P < .0001). These findings from the MMY3003 (POLLUX) trial were presented at the European Hematology Association (EHA) Annual Congress.1
In addition to meeting its primary end point of improved progression-free survival (PFS) and significantly increasing overall response rate (ORR) compared with the standard-of-care, the rate of complete responses (CR) were doubled in the daratumumab arm (43% vs 19%, P < .0001). Daratumumab combination safety was consistent with the known safety profile of daratumumab monotherapy (D) and lenalidomide plus dexamethasone (Rd).
Median PFS has not been reached in the daratumumab arm, median PFS in the standard-of-care arm is 18.4 months, with a median follow-up of 13.5 months. Overall response rate was also significantly increased in the daratumumab arm (93% vs 76%, P < .0001).
The MMY3003 (POLLUX) trial is a phase 3, multinational, open-label, randomized, multicenter, active-controlled study. For this study, 569 patients with multiple myeloma who had received at least 1 prior treatment were randomized to receive either daratumumab combined with lenalidomide and dexamethasone or lenalidomide and dexamethasone alone. Participants received treatment until disease progression, unacceptable toxicity, or another reason to discontinue the study.
The most common treatment-emergent adverse events (TEAEs) in the combination arm vs the standard-of-care arm (DRd/Rd) were neutropenia (59%/43%), diarrhea (43%/25%), fatigue (35%/28%), upper respiratory tract infection (32%/21%), anemia (31%/35%), constipation (29%/25%), cough (29%/13%), thrombocytopenia (27%/27%) and muscle spasms (26%/19%).
Most common Grade 3/4 TEAEs were neutropenia (52%/37%), thrombocytopenia (13%/14%) and anemia (12%/20%). Rate of Grade 3/4 infections was 28% vs 23%, and the most common Grade 3/4 infection (≥5 percent) was pneumonia (8%/8%).
Rates of treatment discontinuation due to TEAEs were similar in the 2 arms (7%/8%). Forty-eight percent of patients experienced daratumumab-associated infusion-related reactions, which were mostly grade 1/2 (grade 3/4, 5%/0%), 92% of which occurred during the first infusion.
The trial was unblinded after its primary end point was reached. Patients in the standard-of-care treatment arm had the option to receive daratumumab after confirmed disease progression, per the recommendation of an Independent Data Monitoring Committee.
1. Janssen Research & Development LLC. Daratumumab significantly extended progression-free survival in combination with lenalidomide and dexamethasone in patients with multiple myeloma [news release]. PR Newswire web site. http://www.prnewswire.com/news-releases/daratumumab-significantly-extended-progression-free-survival-in-combination-with-lenalidomide-and-dexamethasone-in-patients-with-multiple-myeloma-300282833.html. June 10, 2016. Accessed June 15, 2016.