Fiche publication
Date publication
mai 2026
Journal
Therapeutic advances in neurological disorders
Auteurs
Membres identifiés du Cancéropôle Est :
Pr RUBIO Marie Thérèse
,
Dr PAGLIUCA Simona
Tous les auteurs :
Pagliuca S, Jacquet C, Rubio MT, Sorrentino P
Lien Pubmed
Résumé
Chimeric antigen receptor T (CAR-T) cell therapy has transformed outcomes for relapsed/refractory B-cell malignancies and is increasingly reshaping the therapeutic landscape of autoimmune disorders and solid tumors, offering curative potential where options were previously limited. Its broader deployment is, however, constrained by immune-mediated toxicities, chiefly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS spans a heterogeneous spectrum from mild aphasia and tremor to seizures, cerebral edema, coma, and death, and remains difficult to predict prospectively. As CAR-T platforms expand beyond CD19 malignancies, neurotoxicity phenotypes are also broadening beyond classical ICANS. In plasma cell dyscrasias, BCMA-directed CAR-T has been associated with delayed non-ICANS neurotoxicities, including movement and neurocognitive/behavioral symptoms, cranial nerve palsies, and peripheral neuropathic presentations. In parallel, early experiences with CAR-T and related immune effector therapies in autoimmune and neuroimmunologic diseases suggest distinct inflammatory contexts and potentially different neurotoxicity patterns, underscoring the need for indication-specific monitoring and attribution frameworks. Converging data implicate a multilayered pathophysiology involving systemic cytokine surges, disruption of the blood-brain barrier, endothelial dysfunction, and context-dependent trafficking of activated CAR-T cells and other immune effectors into the CNS with baseline neurological vulnerability and the peri-infusion inflammatory milieu likely modulating individual risk. Given the frequency of these complications, an active research effort is underway to identify clinical, functional, and biological signals that could predict and improve their management. However, most biomarkers remain investigational, lacking prospective validation and straightforward clinical utility. This review synthesizes current evidence on the epidemiology, mechanisms, and monitoring of ICANS and emerging non-ICANS syndromes, and offers a fresh perspective on integrated, multimodal risk models to enable more precise stratification and timely intervention across indications.
Mots clés
CAR-T cell neurotoxicity, EEG, ICANS, MNT, neurological biomarkers, virtual brain twin
Référence
Ther Adv Neurol Disord. 2026 05 15;19:17562864261440261
