Immunoglobulin prophylaxis reduces severe infections in multiple myeloma: a systematic review and meta-analysis

Background. Multiple myeloma (MM) is associated with profound immune dysfunction, predisposing patients to severe infections. Immunoglobulin replacement therapy (IgRT) may reduce infection risk, but evidence is heterogeneous and mainly limited to intravenous administration. Its impact, particularly in patients receiving modern therapies such as bispecific T-cell engagers (BiTEs), remains unclear. Methods. We performed a systematic review and meta-analysis of studies comparing MM patients receiving IgRT as preemptive or primary prophylaxis versus those receiving secondary or no IgRT. MEDLINE and LILACS were searched up to December 30, 2025. Both intravenous (IVIg) and subcutaneous (SCIg) routes were included. Comparative studies reporting hazard ratios (HRs) for severe infections or sufficient data to derive them were included, with HRs pooled using random-effects models. Results. Eight studies (358 IgRT-treated, 430 controls) were included, predominantly using IVIg; one study exclusively used SCIg and one included both IVIg and SCIg. IgRT prophylaxis was associated with a 75% reduction in severe infections (pooled HR 0.25, 95% CI 0.13–0.49, p < 0.0001). In BiTEs-treated patients, HR was 0.32 (95% CI 0.18–0.56, p < 0.0001). Results were robust across study designs and sensitivity analyses, with low heterogeneity after leave-one-out analysis. Conclusions. IgRT prophylaxis substantially reduces severe infections in MM, including high-risk BiTEs-treated patients. The benefit is clinically meaningful and mainly reflects IVIg use, though limited evidence suggests SCIg is also effective. These findings support systematic consideration of IgRT in high-risk MM populations, with prospective studies needed to optimize timing, patient selection, and administration.