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 second 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.
Keywords: FAERS; T-cell engagers; adverse events; disproportionality analysis; pharmacovigilance.