Infection Risk Associated with Teclistamab in Relapsed/Refractory Multiple Myeloma

Overview

Teclistamab treatment in relapsed/refractory multiple myeloma patients is linked to a substantial infectious burden, with pooled incidences of 56.5% for any-grade infections and 27.6% for grade ≥3 infections. Infection rates were significantly higher in clinical trial settings compared to real-world evidence, highlighting differences in follow-up duration and prophylactic strategies.

Background

Teclistamab is a BCMA × CD3 bispecific antibody that has demonstrated significant efficacy in heavily pretreated relapsed/refractory multiple myeloma patients. Its mechanism induces T-cell mediated lysis of malignant plasma cells but also causes profound hypogammaglobulinemia due to depletion of healthy plasma cells and late-stage B cells. This results in severe secondary humoral immunodeficiency, increasing susceptibility to infections ranging from common bacterial pathogens to opportunistic infections. Infection is a leading cause of non-hematologic toxicity and treatment interruption in patients receiving teclistamab.

Data Highlights

Key Findings

• Overall pooled incidence of any-grade infections in teclistamab-treated RRMM patients was 56.5%.
• Grade ≥3 infections occurred in 27.6% of patients, indicating a significant risk of severe infections.
• Clinical trial patients experienced significantly higher infection rates than those in real-world cohorts (any-grade: 76.4% vs. 45.4%; grade ≥3: 44.8% vs. 22.8%).
• Infection-related mortality ranged from 0.9% to 7.3%, with COVID-19 and opportunistic infections such as Pneumocystis jirovecii being prevalent causes.
• Heterogeneity in infection rates was influenced by differences in follow-up duration and intravenous immunoglobulin (IVIG) prophylaxis usage.
• Regular IgG monitoring and IVIG replacement in patients with low IgG levels are suggested to optimize safety.

Clinical Implications

Clinicians should be vigilant for infectious complications in RRMM patients receiving teclistamab, given the high incidence of infections and associated mortality. Implementation of standardized infection surveillance protocols, including routine immunoglobulin level monitoring and consideration of IVIG prophylaxis, may mitigate infection risk and improve patient outcomes. Awareness of differences between clinical trial and real-world infection rates is important for risk assessment and management.

Conclusion

Teclistamab therapy in relapsed/refractory multiple myeloma is associated with a substantial infectious burden, necessitating proactive infection monitoring and prophylactic strategies. Integration of real-world data provides a more comprehensive understanding of infection risks in routine clinical practice.

References

1. Systematic Review Registration CRD420261297645