Comprehensive analysis of adverse events associated with T-cell engagers using the FAERS database
Xiangyang Le, Yefu Zhang, Junlong Ma
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.