Infections in Patients Receiving Daratumumab for Newly Diagnosed Multiple Myeloma: A Pooled Analysis of MAIA and ALCYONE

Both the phase 3 MAIA and ALCYONE studies demonstrated significant survival benefit with the addition of daratumumab to standard-of-care lenalidomide and dexamethasone (D-Rd) or bortezomib, melphalan, and prednisone (D-VMP), respectively, versus Rd or VMP alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). Patients with NDMM are highly susceptible to infection; therefore, gaining a greater understanding of infection incidence may help to mitigate future risk. We conducted a pooled analysis of infection incidence, timing, and management strategies from MAIA and ALCYONE. The median (range) age of the pooled population was 72 (40-93) years. Incidence was higher with D-Rd/D-VMP versus Rd/VMP for grade 3/4 (36.9% vs 22.4%) and grade 5 (3.0% vs 1.5%) infections; however, exposure-adjusted incidence rates were generally comparable between groups. Any grade infections led to discontinuation of study treatment in approximately 2% of patients across treatment groups. Of the timing intervals explored, the highest incidence of grade 3/4 infection occurred within the first 6-month interval of study treatment initiation in both groups. Median time to first onset of grade 3/4 infections (per Kaplan-Meier estimates) was 83.3 months and not estimable in D-Rd/D-VMP and Rd/VMP groups, respectively. While rates of D-Rd/D-VMP treatment discontinuation due to infection remained low in MAIA and ALCYONE, clinicians should remain vigilant about infections throughout treatment and follow local guidelines and International Myeloma Working Group recommendations to minimize the risk of infection. ClinicalTrials.gov Identifiers NCT02252172 (MAIA) and NCT02195479 (ALCYONE).