Neurologic adverse effects associated with the use of T-cell engager therapy in multiple myeloma: Insights from FAERS database.

Abstract

e19502 Background: Multiple myeloma (MM) is an incurable malignancy characterized by the clonal proliferation of plasma cells, with relapse/refractory MM (RRMM) posing substantial therapeutic challenges despite recent advancements. T-cell engager (TCE) therapies, including teclistamab, talquetamab, and elranatamab, have emerged as promising options for heavily pre-treated RRMM. However, these agents are associated with potentially life-threatening adverse events (AEs), particularly neurotoxicity, the burden of which remains poorly understood. This study aimed to explore and better define the burden of neurotoxicity associated with TCE therapy. Methods: This study retrospectively analyzed the FDA Adverse Event Reporting System (FAERS) database to characterize neurological AEs associated with TCE therapy in MM patients, including teclistamab, talquetamab and elranatamab, with data collected up to 30 th December 2024. Neurological AEs , including immune effector cell-associated neurotoxicity syndrome (ICANS) and others, were were assessed through descriptive analysis. Results: A total of 2,832 AEs were reported, with 37.3% from male patients, 32.1% from female patients, and 30.6% with missing gender data. Most reports (90.4%) came from healthcare professionals, 9.2% from consumers, and 0.3% had unspecified sources. Among 2,832 identified AEs, neurological AEs comprised 22.7% (645 events), with teclistamab accounting for the majority of both total (63.4%) and neurological AEs (56.6%) followed by talquetamab (19.6% total and 31% neurological AEs) and elranatamab (17% total and 12.4% neurological AEs). ICANS was the most frequently reported neurological AE (30%), with teclistamab linked to 140 events, followed by talquetamab (28 events) and elranatamab (26 events). Non-ICANS neurotoxicity (41 events) and peripheral neuropathy (46 events) were predominantly associated with teclistamab. Additionally, talquetamab was notable for a high prevalence of taste disorders (145/154 events). Facial nerve paralysis was reported in six patients, with elranatamab accounting for four cases. Mortality was highest with teclistamab, accounting for 74.7% of reported deaths followed by elranatamab (17.8%) and talquetamab (7.5%). Conclusions: Neurological AEs represent a significant component of the toxicity profile of TCEs in MM, particularly with teclistamab, underscoring the need for vigilant monitoring and early management of complications. Future research should focus on identifying predictive biomarkers and optimizing management strategies to enhance patient outcomes in TCE therapy for RRMM.