Burden of infections and preventive strategies in patients with relapsed/refractory multiple myeloma treated with bispecific antibodies.

Bispecific antibodies(BsAbs) are a novel class of therapy for relapsed/refractory multiple myeloma (RRMM), leading to deep and durable responses in heavily pretreated patients. Their use is associated with a high burden of infections, particularly with anti-BCMA-targeting agents. This retrospective, single-center study included 50 RRMM patients treated with anti-BCMA or anti-GPRC5D BsAbs, of whom 13 received both agents because of disease progression. Standard prophylactic strategies included vaccination, antimicrobial prophylaxis, and, in selected patients, subcutaneous immunoglobulin (SCIg). Overall, 78% of patients received prior vaccinations and those with ≥3-4 vaccines exhibited the lowest infection-related mortality (23.4%, respectively 6.7%). We analyzed 121 infectious episodes recorded during the study period, of which 45.5% were severe (grade ≥3). The respiratory tract was the most affected site (65%), by viral (43%) and bacterial (45%) etiologies. Anti-BCMA BsAb were associated with a higher incidence and severity of infections, as well as a shorter median time to first infection compared with anti-GPRC5D therapy (2.3 vs 3.8 months). Infectious complications occurred throughout the course of therapy, with the highest risk observed early after treatment initiation, while remaining clinically relevant during prolonged follow-up. Infection-related mortality was the second leading cause of death (34%), after disease progression. Multivariable analyses showed that male sex and patients with high-risk disease were associated with increased infection risk.