Pondrelli Federica, Muccioli Lorenzo, Mason Federico, Zenesini Corrado, Ferri Lorenzo, Asioli Gian Maria, Rossi Simone, Rinaldi Rita, Rondelli Francesca, Nicodemo Marianna, D'Angelo Roberto, Barone Valentina, Sambati Luisa, Pensato Umberto, Zinzani Pier Luigi, Casadei Beatrice, Bonifazi Francesca, Maffini Enrico, Pierucci Elisabetta, Cortelli Pietro, Tinuper Paolo, Bisulli Francesca, Guarino Maria
IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
J Neurol. 2025 Apr 25;272(5):360. doi: 10.1007/s00415-025-13102-3.
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a potentially fatal complication of CD19-directed CAR T-cell therapy. The aim of this study was to investigate the role of EEG as a predictive biomarker of ICANS.
In this prospective, monocentric, cohort study, consecutive refractory B-cell non-Hodgkin lymphoma patients undergoing CAR T-cell therapy had EEG assessments at fixed time points pre- and post-infusion. The risk of ICANS was evaluated according to EEG findings detected qualitatively, using a grading scale ranging from 0 (normal) to 3 (severely abnormal), and quantitatively, using power spectral and connectivity measures.
307 EEGs from 68 patients have been qualitatively evaluated, of whom 238 were eligible for quantitative analysis. Neurotoxicity manifested in 22/68 (32.4%) patients. Pre-infusion EEG abnormalities (grade 1 and 2) were qualitatively detected in 8/68 (11.7%) patients, emerging as a risk factor for ICANS [HR 5.8 (95%CI 2.6-12.9)]. Quantitative analysis of pre-infusion EEGs did not yield significative results. Post-infusion qualitative EEG abnormalities were associated to a higher risk of ICANS development [HR 11.6 (4.4-30.5) for grade 2; HR 9.7 (2.6-36.6) for grade 3]. Concerning the quantitative analysis, in post-infusion EEGs higher theta energy [HR 1.10 (1.03-1.16)] and delta + theta/alfa ratio [HR 1.37 (1.11-1.67)] were associated to higher risk of ICANS, while higher beta energy resulted protective [HR 0.91 (0.85-0.97)].
Our study establishes EEG as a predictive tool for identifying patients at risk for ICANS before CAR T-cell infusion, who may benefit from prophylactic treatments, and anticipating ICANS onset following infusion, enabling early intervention.
免疫效应细胞相关神经毒性综合征（ICANS）是CD19导向的嵌合抗原受体T细胞（CAR T）疗法的一种潜在致命并发症。本研究旨在探讨脑电图（EEG）作为ICANS预测生物标志物的作用。
在这项前瞻性、单中心队列研究中，连续接受CAR T细胞治疗的难治性B细胞非霍奇金淋巴瘤患者在输注前后的固定时间点进行EEG评估。根据定性检测到的EEG结果评估ICANS风险，使用从0（正常）到3（严重异常）的分级量表，以及通过功率谱和连接性测量进行定量评估。
对68例患者的307份EEG进行了定性评估，其中238份符合定量分析条件。22/68（32.4%）例患者出现神经毒性。8/68（11.7%）例患者在输注前定性检测到EEG异常（1级和2级），这成为ICANS的一个危险因素[风险比（HR）5.8（95%置信区间2.6 - 12.9）]。输注前EEG的定量分析未得出显著结果。输注后定性EEG异常与ICANS发生风险较高相关[2级的HR为11.6（4.4 - 30.5）；3级的HR为9.7（2.6 - 36.6）]。关于定量分析，在输注后EEG中，较高的θ能量[HR 1.10（1.03 - 1.16）]和δ + θ/α比率[HR 1.37（1.11 - 1.67）]与ICANS风险较高相关，而较高的β能量具有保护作用[HR 0.91（0.85 - 0.97）]。
我们的研究将EEG确立为一种预测工具，用于在CAR T细胞输注前识别有ICANS风险的患者，这些患者可能从预防性治疗中获益，并在输注后预测ICANS的发作，从而实现早期干预。
