Temporal trends in infectious risk among multiple myeloma patients treated with daratumumab: A meta‐analysis

Summary

Anti‐cluster of differentiation 38 (Anti‐CD38) monoclonal antibodies such as daratumumab are widely used in multiple myeloma (MM), yet the timing and magnitude of infectious risk remain incompletely defined. We performed an individual patient‐level meta‐analysis of six randomized trials ( N  = 2989) comparing daratumumab‐ versus non‐daratumumab–containing regimens in newly diagnosed and relapsed/refractory MM, assessing infectious events over 2 years. Daratumumab‐treated patients had higher rates of any‐grade (79% vs. 61%) and grade ≥3 infections (29% vs. 20%) than controls, with risk peaking in the first 3 months (42% vs. 36%, p  = 0.001) before plateauing. After adjustment, daratumumab was independently associated with grade ≥1 (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.10–1.57), respiratory (OR 1.38, 95% CI 1.11–1.71) and grade ≥3 (OR 1.47, 95% CI 1.08–2.00) infection by 3 months. Daratumumab‐treated patients had a higher rate of infection over 2 years (adjusted incidence rate ratio 1.60, 95% CI 1.47–1.73) and more frequently experienced recurrent infections (33% vs. 22% with multiple any‐grade infections; 11% vs. 7% with multiple grade ≥3 infections). Preventive strategies were underused, with <20% of patients with severe respiratory infections receiving immunoglobulin replacement. These findings identify an early window of infectious vulnerability with daratumumab and support temporally targeted prevention and monitoring strategies in contemporary MM care.