Neurologic Adverse Events Associated With T-cell Engager Therapy in Multiple Myeloma: A Pharmacovigilance Study

Introduction and aim Relapse/refractory multiple myeloma (RRMM) presents significant therapeutic challenges despite recent advances. T-cell engager (TCE) therapies, such as teclistamab (TL), talquetamab (TQ), and elranatamab (ER), have emerged as promising options. However, these agents are associated with potentially life-threatening adverse effects (AEs), particularly neurological adverse effects (NAEs). This study aimed to assess the spectrum, reporting patterns, and relative likelihood of NAEs occurrence across TL, TQ, and ER. Methods We performed a retrospective analysis of the 2024 FDA Adverse Event Reporting System (FAERS) database using descriptive statistics and disproportionality analysis methods, including reporting odds ratio (ROR) and Empirical Bayes Geometric Mean (EBGM). Results Among the 1921 identified total AE cases, NAEs comprised 27.6% (530 cases), with TL accounting for the majority of the NAEs: 248 (46.79%) cases, followed by TQ: 201 (37.9%) cases, and ER: 81 (15.3%) cases. TQ demonstrated the greatest NAEs reporting proportion (RP) (39.2%), followed by TL (26.1%), and ER (17.6%). Among all reported NAEs, 159 events (26.9%) were immune effector cell-associated neurotoxicity syndrome (ICANS), while non-ICANS NAEs comprised 433 events (73.1%). ICANS were most frequently reported with TL (35.8% of NAEs), followed by ER (35.3%) and TQ (14%). TL also had the highest proportion of deaths among AE reports (24.4%). Disproportionality analysis revealed that TQ had the highest association with NAEs (ROR: 2.13; EBGM: 1.70), while ER had the lowest (ROR: 0.49; EBGM: 0.57). TL did not demonstrate a strong disproportionality signal (ROR: 0.85; EBGM: 0.92). Conclusion NAEs are a substantial part of the toxicity profile of TCEs in RRMM, particularly in the context of TL. These findings underscore the need for proactive neurologic monitoring and further research to identify predictive markers and improve management strategies.