超越典型免疫效应细胞相关神经毒性综合征：描述 CAR-T 细胞治疗中非免疫效应细胞相关神经毒性综合征的神经系统并发症——一项回顾性分析

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory hematologic malignancies. While immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-recognized complication, expanding clinical use has revealed distinct non-ICANS neurological complications that challenge standard diagnostic and management approaches. We characterize the clinical features and outcomes of these non-classic presentations.

A retrospective analysis was conducted on 357 patients receiving commercial CAR-T therapy for non-Hodgkin lymphoma or multiple myeloma at a single academic center (2015-2025). Non-ICANS neurological complications were defined by neurologic deficits, movement disorders, or neurocognitive syndromes occurring in the absence of global encephalopathy (ICE scores 9-10). Institutional protocol included baseline neurology evaluation and brain MRI.

Non-ICANS complications occurred in 17 patients (4.76%). Manifestations included focal neuropathies or myelopathy ( n = 5), progressive leukoencephalopathy ( n = 4), neuropsychiatric symptoms ( n = 3), Parkinsonism ( n = 2), and cranial nerve palsies ( n = 4). Compared to the institutional median for classic ICANS (7 days), non-ICANS demonstrated a prolonged median duration of 14 days (range, 4-365+ days). Abnormal brain MRI findings were present in 5 of 15 (33.3%) cases with post-treatment brain MRI, manifesting commonly as T2/FLAIR hyperintensities in the white matter. Cerebrospinal fluid (CSF) immunomonitoring in a subset of cases ( n = 2) revealed an enrichment of CAR T-cells compared to peripheral blood.

Non-ICANS neurological complications represent a distinct clinical subset characterized by atypical findings, neuroimaging abnormalities, and/or protracted recovery. Increased clinical vigilance and tailored diagnostic approaches are essential to mitigate long-term morbidity, as standard screening tools fail to capture these focal neurotoxicities.