Immune Complications Increase Infection Risk in Advanced Multiple Myeloma Therapies

Chimeric Antigen Receptor (CAR) T-cell and bispecific antibody (BsAb) therapies have fundamentally changed the treatment landscape for multiple myeloma (MM), offering patients durable responses and new hope for disease control. However, these therapies are associated with a heightened risk of infections and immune dysregulation, creating significant challenges for clinicians and pharmacists managing these patients.

Data presented at IDWeek 2025 emphasize the importance of focused strategies for infection prevention and vigilant monitoring to maximize patient safety and improve survival outcomes.

An analysis using the FDA Adverse Event Reporting System (FAERS) database evaluated infection incidence and immune-related complications in patients receiving CAR-T therapies—Ciltacabtagene and Idecabtagene—and BsAb constructs, including Teclistamab, Talquetamab, and Elranatanab. The study specifically assessed infections in the context of immune complications, such as Cytokine Release Syndrome (CRS), Immune-Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and Immune-Effector Cell-Associated Hemophagocytic Lymphohistiocytosis (IECHLH).

Overall, the study identified a total incidence of infections and immune dysregulation of 14.4% in CAR-T recipients compared with 32.2% in the BsAb group, a statistically significant difference (P < .01). Notably, the types of infections varied by therapy. In the CAR-T cohort, hypogammaglobulinemia was most frequent (1.31%), followed closely by fungal infections (1.20%). In contrast, BsAb-treated patients most commonly experienced cytomegalovirus infections (1.79%), followed by hypogammaglobulinemia (1.58%). These findings highlight the distinct immune risk profiles associated with each therapy.

Importantly, infections occurring in conjunction with immune complications such as CRS, ICANS, or IECHLH were more common in CAR-T recipients than in those receiving BsAb therapy (20.0% vs 6.1%, P < .01). The study also calculated odds ratios for infection risk in the presence of immune dysregulation, illustrating the heightened vulnerability of CAR-T patients when these syndromes occur. These results were visualized in a forest plot, emphasizing the clinical impact of immune-related events on infection risk and subsequent patient outcomes.

The findings underscore a critical issue for pharmacy practice: while CAR-T and BsAb therapies offer remarkable anti-myeloma activity, infections remain the leading cause of non-relapse mortality in this population. Immune complications further complicate management, reinforcing the need for proactive strategies, including risk assessment, monitoring, and tailored anti-infective prophylaxis. Pharmacists play an essential role in this framework, providing guidance on antimicrobial selection, dosing adjustments in immunocompromised patients, and monitoring for early signs of infection or immune-mediated complications.

As CAR-T and BsAb therapies continue to expand in clinical use, this study highlights the urgent need for consensus guidelines on infection prevention and management. Interdisciplinary collaboration—including hematologists, infectious disease specialists, and pharmacists—will be critical to optimizing outcomes, mitigating risks, and ensuring the full therapeutic potential of these transformative therapies is realized.

In summary, while CAR-T and BsAb therapies are redefining MM treatment, infections and immune-related complications remain significant clinical challenges. Focused strategies for infection prevention and vigilant monitoring are essential to maximizing patient safety and improving survival outcomes in this high-risk population.

REFERENCES

Thiruvadi V, Mahadevan A, Asif S, Francisco D. (P-2165) Comparison of Incidence Reporting and Outcomes of Infections in Chimeric Antigen Receptor T (CART) Cell Therapy and Bispecific Antibodies (BsAb) Therapy for Multiple Myeloma: A Retrospective Pharmacovigilance Study. Presented at: IDWeek 2025. October 19-22, 2025. Atlanta, Georgia. Abstract P-2165.