Comprehensive analysis of adverse events associated with T-cell engagers using the FAERS database.

Abstract

Background: T-cell engagers (TCEs) are transformative immunotherapies with significant potential in treating hematologic malignancies and solid tumors. However, their real-world safety profiles remain inadequately characterized.

Research design and methods: Using the FDA Adverse Event Reporting System (FAERS) database (October 2019 - September 2024, 8,747,158 reports), we analyzed adverse events (AEs) associated with nine TCEs. Disproportionality analysis identified overreported AEs, with 11,963 unique reports analyzed after deduplication.

Results: Blinatumomab was the most reported TCE (n = 4,950), and Tarlatamab the least (n = 185). Predominant AEs included immune system disorders, particularly cytokine release syndrome (IC₀₂₅ range: 6.08 - 7.47). Drug-specific signals included reproductive system and breast disorders (IC₀₂₅: 2.74) and vascular disorders (IC₀₂₅: 2.25) with Tebentafusp, renal and urinary disorders with Epcoritamab (IC₀₂₅: 1.84), and eye disorders with Elranatamab (IC₀₂₅: 1.81). Novel AEs were also uncovered, including secondary malignant neoplasms, vasogenic cerebral edema with Mosunetuzumab (IC₀₂₅: 5.77, ROR₀₂₅: 56.29), and hydronephrosis with Epcoritamab (IC₀₂₅: 7.50, ROR₀₂₅: 180.70). Early-onset events (0.5 - 9.5 days) were linked to four TCEs, while delayed-onset events (>20 days) were linked to five others.

Conclusions: This study highlights diverse AE profiles of TCEs, providing insights for clinicians to optimize their safe use in practice.