Post-marketing safety surveillance of tarlatamab: a real-world pharmacovigilance study based on the FAERS database

As the first-in-class delta-like ligand 3/cluster of differentiation 3 bispecific T-cell engager approved globally for extensive-stage small cell lung cancer, tarlatamab still lacks comprehensive post-marketing safety data from real-world settings beyond clinical trials. This study employs the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to conduct a comprehensive evaluation of its safety profile, identifying potential risk signals and variations among subpopulations. A retrospective analysis was conducted using data from the FAERS prior to Q2 2025. Reports listing tarlatamab as the primary suspect drug were included. Signal detection employed quadruple disproportionality analysis (reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker). Adverse events (AEs) were standardized using the Medical Dictionary for Regulatory Activities v27.1. Subgroup analyses focused on sex, age, and clinical outcomes. Analysis of 676 tarlatamab-associated AE reports revealed extremely strong signals for core on-target toxicities: cytokine release syndrome (CRS) (ROR = 618.54) and immune effector cell-associated neurotoxicity syndrome (ICANS) (ROR = 1014.66). New safety signals included tumor lysis syndrome (TLS) (ROR = 48.15) and respiratory failure (ROR = 6.45), both of which exhibited significant disproportionality. Sex-based analysis identified significantly higher CRS risk in females versus males (ROR = 947.46 vs 400.82), while mortality reports were more prominent in males (ROR = 2.81). The overall onset time for all AEs exhibited an early failure pattern, with a median onset time of 3 days (interquartile range, 1-10). Clinical outcomes analysis indicated death events in 12.9% of cases and hospitalization requirements in 20.9%. Leveraging FAERS, this first comprehensive real-world characterization of tarlatamab safety confirms core immune-related toxicities (CRS, ICANS) and identifies new signals (TLS, respiratory failure), with sex- and age-associated risk differences. As spontaneous-report signals are inherently hypothesis-generating, causality requires validation in robust pharmacoepidemiologic studies; meanwhile, early detection and supportive care are essential to optimize the benefit-risk profile as use expands.