IVIG prophylaxis should be initiated following bispecific antibody therapy in multiple myeloma regardless of IgG levels.

Bispecific antibodies (bsAbs) such as teclistamab, elranatamab, linvoseltamab, and talquetamab have impressive efficacy in multiple myeloma (MM) but come with substantial infectious risks that do not dissipate over time. Immunoglobulin replacement therapy (IgRT), which includes intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG), may lower these risks. In this Viewpoint, we contrast primary IgRT prophylaxis (initiation regardless of IgG levels) with preemptive IgRT treatment (initiation only once IgG levels fall below a certain threshold) in this setting. We make evidence-based arguments for primary prophylaxis as a safer and simpler approach compared to preemptive IgG-guided IgRT. We also discuss strategies to improve the cost-effectiveness of IVIG and SCIG across the world. Given the overwhelmingly favorable benefit-risk profile of IgRT coupled with the limitations inherent to IgG measurements in MM, withholding IgRT access based on arbitrary IgG thresholds is neither scientifically sound nor clinically appropriate for patients with MM receiving bsAb therapy.