Immunoglobulin prophylaxis should be initiated after bispecific antibody therapy in multiple myeloma, regardless of IgG levels

Abstract

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 IV and subcutaneous (SC) immunoglobulins, 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 than preemptive IgG-guided IgRT. We also discuss strategies to improve the cost-effectiveness of IV and SC immunoglobulins 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 who are receiving bsAb therapy.

Figure 1.

Future areas of research for IgRT with bsAb therapy in MM. ∗For example, higher IgRT dose intensity for patients who are receiving BCMA-targeted bsAbs, bsAbs in combination with other drugs, and/or concurrent lymphopenia; ^†for example, planned IgRT discontinuation once IgG troughs consistently exceed a certain threshold (eg, 400 mg/dL); ^‡for example, planned IgRT discontinuation after a fixed number of months (eg, after 6 months) or once bsAb dosing frequency is sufficiently de-escalated (eg, to once every 4 weeks or less frequently).