Epidemiology and Risk Factors for Infection in Multiple Myeloma Patients Treated With Bispecific Antibodies

Bispecific antibodies (BsAbs) have revolutionized multiple myeloma (MM) treatment but are associated with infectious complications. This study aims to characterize the incidence, microbiological patterns, and risk factors for infection in this population.

We conducted an observational cohort study of adult MM patients treated with BsAbs at a single center between 2020 and 2025. Clinical and microbiological features of different types of infection were analyzed. Risk factors for recurrent events were assessed by Cox regression.

Among 92 patients receiving 98 BsAb courses, 352 infectious episodes were identified (incidence rate: 3.20 episodes per BsAbs course-year). Most common syndromes were respiratory (71.3%) and digestive (11.9%), with predominant viral etiology (62.8%). Severe (grade ≥3) infections occurred in 45.9% of courses. Anti-BCMA BsAbs carried a higher infection risk than anti-GPRC5D therapy (aHR: 1.41, 95% CI: 1.02-1.94; P-value = 0.035). Previous BsAb exposure (aHR: 1.75, 95% CI: 1.23-2.50; P-value = 0.002), allogeneic hematopoietic stem-cell transplantation (aHR: 1.59, 95% CI: 1.12-2.26; P-value = 0.010), and development of immune effector cell-associated neurotoxicity syndrome (ICANS) (aHR: 3.23, 95% CI: 1.27-8.19; P-value = 0.001) increased the risk of infection. Intravenous immunoglobulin (IVIg) therapy was protective (aHR: 0.68, 95% CI: 0.53-0.86; P-value = 0.002). Concurrent infections were documented in only 6.8% of first episodes of cytokine release syndrome (CRS).

BsAb therapy for MM is associated with a high infection burden, predominantly respiratory and gastrointestinal. Risk is driven by cumulative immunosuppression and therapy for ICANS, while IVIg therapy reduces this susceptibility. Infections are uncommon during CRS episodes.