Work

Neurologist-focused workflows for immune effector cell-associated neurotoxicity syndrome in CAR T-cell therapy and CD3-engaging bispecific antibodies

Year: 2026

Type: article

Abstract: Objective: To synthesize current evidence into a neurologist-focused workflow for early recognition, bedside monitoring, diagnostic triage, mitigation, and therapy-specific surveillance of immune effector cell-associated neurotoxicity syndrome (ICANS). Methods: PubMed/MEDLINE, Scopus, Web of Science Core Collection, and Google Scholar were searched in English from inception through 25 March 2026. Of 201 records, 18 duplicates were removed, 183 were screened, 157 full texts were assessed, and 26 studies were included in a narrative synthesis. The selection process was reported using applicable PRISMA 2020 elements and the narrative presentation was evaluated using SANRA. Results: Evidence supports early neurologic co-management in selected high-risk patients, serial language- and attention-sensitive bedside assessment, and clinically triggered rather than routine electroencephalography. Pilot neurocognitive data suggest that subtle decline may precede deterioration on the Immune Effector Cell-Associated Encephalopathy (ICE) score. Bispecific-antibody programs generally show lower neurotoxicity burdens than many CAR T-cell platforms but create repeated risk windows around step-up dosing and outpatient transition. Delayed B-cell maturation antigen (BCMA)-associated movement and neurocognitive syndromes remain an important safety signal, although therapeutic evidence is largely observational or case based. Conclusion: The evidence supports documenting a baseline neurologic phenotype, performing serial bedside monitoring, deploying electroencephalography and neuroimaging when results may change management, and maintaining product-specific vigilance for delayed syndromes. Tiered pathways are needed for community and resource-limited settings.

Source: Frontiers in Neurology

DOI: 10.3389/fneur.2026.1903348