Preemptive Immunoglobulin Prophylaxis Reduces Infections in Patients Treated With Anti-BCMA Bispecific Antibodies

Bispecific antibodies (BsAbs) targeting B-cell maturation antigen (BCMA) have improved outcomes for patients with relapsed/refractory multiple myeloma (MM). However, hypogammaglobulinemia driven by normal plasma cell depletion expose patients to high risk of infections. Immunoglobulin (IG) prophylaxis is recommended in patients receiving BsAbs and IgG level < 400 mg/dL. Real world evidence of the impact of preemptive IG prophylaxis remains limited.

We conducted a retrospective, single-center study including all consecutive MM patients receiving anti-BCMA BsAbs between December 2020 and May 2024. Patients started treatment before June 1, 2023, received IG as secondary prophylaxis. In contrast, patients treated after this date received preemptive IG prophylaxis if IgG level < 400 mg/dL in alignment with international recommendations.

From Dec 2020 to June 2023, 42 patients received secondary IG prophylaxis with a median initiation time of 7.8 months from first anti-BCMA BsAb injection. From July 2023 to May 2024, 24 received preemptive IG prophylaxis with a median time to initiation of 1.6 months. During a 9-months observation period, patients in the preemptive IG group experienced a significant 66% reduction in all-grade infections (HR 0.34; 95% CI, 0.19-0.60; P = .0002) and 76% reduction in severe infections (HR 0.24; 95% CI, 0.08-0.69; P = .0084). Infections also occurred earlier without preemptive supplementation.

This study supports the benefit of early and preemptive IG supplementation in reducing severe and non-severe infections in patients treated with anti-BCMA BsAbs. Prospective studies are needed to confirm these findings, assess cost-effectiveness, and define optimal IG duration and route administration.