Toxicity and Non-Relapse Mortality of BCMA-Targeted T Cell Therapies in Multiple Myeloma

Overview

This FAERS database analysis reveals distinct toxicity profiles and non-relapse mortality (NRM) rates among FDA-approved BCMA-directed therapies for relapsed/refractory multiple myeloma. Teclistamab showed the highest rates of life-threatening events, hospitalizations, and NRM, primarily driven by infections, while ide-cel had the highest rates of cytokine release syndrome (CRS) and non-ICANS neurotoxicity but the lowest NRM.

Background

BCMA-directed T cell therapies, including CAR T-cell products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), and the bispecific antibody teclistamab, have transformed treatment options for relapsed/refractory multiple myeloma. Despite their efficacy, these therapies carry risks of serious toxicities such as CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), other neurotoxicities, and infections, which contribute to morbidity and mortality. Variability exists in attributing adverse events and mortality to these therapies in clinical trials. The FDA Adverse Event Reporting System (FAERS) provides real-world data on adverse events and mortality related to these agents.

Data Highlights

Key Findings

• Teclistamab had the highest hospitalization (53.5%), life-threatening events (11.3%), and death rates (22.1%) among the three therapies.
• Ide-cel showed the highest rates of CRS (16.1%) and non-ICANS neurotoxicity (10.1%) with the highest reporting odds ratios (ROR) for these toxicities.
• Non-ICANS neurotoxicities such as Bell’s palsy and Parkinsonism were predominantly reported with cilta-cel, consistent with clinical trial data.
• Infections including pneumonia, sepsis, COVID-19, and CMV reactivation were most common with teclistamab and contributed significantly to its higher non-relapse mortality (NRM).
• Odds ratio for NRM was lowest with ide-cel (0.53), intermediate with cilta-cel (0.99), and highest with teclistamab (1.72), reflecting differing toxicity and patient selection profiles.
• Distinct toxicity profiles reflect differences between CAR T-cell therapies and bispecific antibodies, including vein-to-vein time and patient eligibility criteria.

Clinical Implications

Clinicians should be aware of the distinct toxicity profiles when selecting BCMA-targeted therapies for multiple myeloma patients. CAR T-cell therapies like ide-cel and cilta-cel carry higher risks of CRS and neurotoxicity, requiring vigilant monitoring and management. In contrast, teclistamab, an off-the-shelf bispecific antibody, is associated with higher infection rates and non-relapse mortality, necessitating proactive infection surveillance and prevention strategies. Patient selection and organ function assessment remain critical to optimize outcomes and minimize treatment-related mortality.

Conclusion

This FAERS analysis underscores the unique safety considerations of BCMA-directed T cell therapies in multiple myeloma, highlighting the need for tailored monitoring and supportive care strategies to mitigate toxicities and improve patient outcomes. Understanding these differences can guide therapy choice and risk management in clinical practice.

References

1. FDA Adverse Event Reporting System (FAERS) Database Analysis
2. Clinical Trials and Safety Data of BCMA-Directed Therapies