Adverse neurological events associated with bispecific T cell engagers in oncology: a real-world study

With the increasing use of bispecific T cell engagers (BiTEs) in anti-tumor immunotherapy, the associated adverse reactions pose significant challenges to clinical application. Nervous system toxicity (NST) is one of the notable adverse events associated with this class of drugs. This study aims to provide a comprehensive analysis of BiTE-induced nervous system adverse events. Improving the diagnosis and monitoring of these adverse events is crucial for the early identification and treatment of NSTs.

We utilized the FAERS database to analyze NSTs associated with BiTEs reported between January 2004 and September 2025. Positive safety signals of the drugs were assessed using four commonly applied disproportionality analysis methods. In addition, the time to onset of drug-induced adverse reactions was evaluated.

A total of 15,558 patients who developed NSTs during BiTE therapy were included in this study. The average age at NST onset was 51.12 ± 24.44 years. The incidence was 21.19% higher in men than in women (6,139 men vs. 5,065 women), with the United States reporting the highest proportion of cases (50.68%). Among the BiTEs analyzed, blinatumomab accounted for the highest number of reported cases (49.63%). The NSTs observed include immune effector cell-associated neurotoxicity syndrome and other forms of neurotoxicity. Tremor, seizures, and nervous system disorders were reported more frequently with blinatumomab. In the comparative analysis of drug induction time, glofitamab exhibited the longest induction time [82.00 days (range, 1∼1190)], whereas tarlatamab showed the shortest time [16.70 days (range, 1∼141)].

BiTEs have the potential to induce significant adverse events within the central nervous system and may exacerbate pre-existing conditions. Given the increasing utilization of BiTEs, it is essential to integrate resources such as the FAERS database to effectively monitor adverse reactions associated with these novel therapeutic agents.