Guidelines for Infection Management in Multiple Myeloma Patients on Bispecific Antibody Therapy

Overview

Bispecific antibodies (BsAbs) represent a novel immunotherapy for multiple myeloma (MM) with promising efficacy but increased infection risks. An expert panel developed consensus recommendations for infection diagnosis, prophylaxis, and management in MM patients receiving BsAbs, based on a systematic literature review and clinical experience.

Background

Multiple myeloma is a hematologic malignancy characterized by immune dysfunction, leading to increased susceptibility to infections. BsAbs target MM-specific antigens and activate T cells to induce tumor cell lysis, with agents such as teclistamab and elranatamab showing clinical promise. However, BsAb therapy is associated with adverse events including cytopenias, hypogammaglobulinemia, and immune-related toxicities that elevate infection risk. Given the poor prognosis of triple-class refractory MM and the emergence of BsAbs as treatment options, guidance on infection management is critical.

Data Highlights

Infection rates with BCMA-targeting BsAbs range from 33% to 76%, reflecting increased susceptibility due to immune modulation. Clinical trials such as MajesTEC-1 for teclistamab included 165 patients, providing substantial data on infection incidence. Opportunistic infections like pneumocystis jirovecii pneumonia, cytomegalovirus reactivation, and hepatitis B virus reactivation have been reported. The panel graded recommendations from empirical to obligatory based on evidence strength.

Key Findings

• BsAbs increase infection risk in MM patients due to immune system impairment and therapy-related cytopenias and hypogammaglobulinemia.
• Common adverse events contributing to infections include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.
• Opportunistic infections such as PJP, CMV, and HBV reactivation are notable concerns requiring monitoring and prophylaxis.
• Current infection rates with BCMA-targeted BsAbs vary widely, emphasizing the need for vigilant infection surveillance.
• Consensus recommendations were developed by a panel of 13 experts using systematic literature review and clinical experience, with graded levels of evidence.

Clinical Implications

Clinicians should implement proactive infection monitoring and prophylactic strategies in MM patients receiving BsAb therapy, particularly for opportunistic infections. Awareness of immune-related adverse events and their management is essential to mitigate infection risk. These guidelines provide a framework to optimize patient outcomes during BsAb treatment.

Conclusion

Bispecific antibody therapy offers a promising treatment for relapsed/refractory multiple myeloma but carries a significant infection risk. Expert consensus guidelines support tailored infection prevention and management to improve patient safety and treatment success.

References

1. European Medicines Agency 2022 -- Accelerated approval of teclistamab
2. U.S. Food and Drug Administration 2022 -- Accelerated approval of teclistamab
3. International Myeloma Workshop 2022 -- Expert panel consensus on BsAb infection management