Modoni Anna, Vollono Catello, Galli Eugenio, Capriati Luca, Sorà Federica, Hohaus Stefan, Servidei Serenella, Piccirillo Nicola, Calabresi Paolo, Sica Simona
UOC Neurologia, Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Dipartimento Universitario di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy.
Brain Behav. 2025 Sep;15(9):e70891. doi: 10.1002/brb3.70891.
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is an innovative and effective treatment for patients with B-cell hematological malignancies. Despite its high efficacy, it has been associated with the development of acute toxicities that can be severe or even fatal. Indeed, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can induce significant morbidity and require close monitoring. Identification of clinical and laboratory markers able to predict the occurrence of ICANS may allow prompt recognition and more effective management strategies.
Here, we report a retrospective study on a cohort of 81 Italian adult patients treated in our hospital between September 2019 and April 2024. We reviewed all clinical, demographic, laboratory, and neurophysiological data in order to identify potential predictors.
The results of the multivariate analysis confirmed that ICANS typically occurred less frequently in younger patients, especially when treated with 41BB co-stimulated CAR-T. Baseline EEG abnormalities are confirmed to be a fundamental predictor of neurotoxicity. Interestingly, we identified GammaGT as a new, statistically significant marker of ICANS. This represents a novel finding, probably related to the important role of GammaGT also in neuroinflammation.
Our results need to be confirmed in a larger cohort of patients in order to eventually be integrated into current clinical practice and management of patients undergoing CAR-T.
抗CD19嵌合抗原受体（CAR）T细胞疗法是治疗B细胞血液系统恶性肿瘤患者的一种创新且有效的方法。尽管其疗效显著，但它与可能严重甚至致命的急性毒性反应的发生有关。事实上，细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）可导致严重发病，需要密切监测。识别能够预测ICANS发生的临床和实验室标志物，可能有助于及时识别并采取更有效的管理策略。
在此，我们报告一项对2019年9月至2024年4月期间在我院接受治疗的81名意大利成年患者队列的回顾性研究。我们回顾了所有临床、人口统计学、实验室和神经生理学数据，以确定潜在的预测因素。
多变量分析结果证实，ICANS在年轻患者中通常发生频率较低，尤其是接受41BB共刺激CAR-T治疗时。基线脑电图异常被确认为神经毒性的一个重要预测因素。有趣的是，我们将γ-谷氨酰转移酶（GammaGT）确定为ICANS的一个新的具有统计学意义的标志物。这代表了一项新发现，可能与GammaGT在神经炎症中的重要作用有关。
我们的结果需要在更大的患者队列中得到证实，以便最终纳入接受CAR-T治疗患者的当前临床实践和管理中。
