基线认知和神经学状态不会改变侵袭性B细胞淋巴瘤CAR-T细胞治疗中免疫效应细胞相关神经毒性综合征（ICANS）的发生情况。

Baseline Cognitive and Neurological Status Does Not Modify the Occurrence of ICANS in CAR T-Cell Therapy for Aggressive B-Cell Lymphoma.

作者信息

Ursu Renata, Barsan Claudia, Di Blasi Roberta, Belin Catherine, Cuzzubbo Stefania, El Soudany Mohamed, Cristinelli Caterina, Sivapragassame Raghunath, Ouedrani Amani, Thieblemont Catherine, Caillat-Zucman Sophie, Carpentier Antoine F

机构信息

Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Service de Neurologie, Paris, France.

Université Paris Cité, Paris, France.

出版信息

Eur J Neurol. 2025 Jun;32(6):e70236. doi: 10.1111/ene.70236.

DOI:10.1111/ene.70236

PMID:40542557

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12181688/

Abstract

BACKGROUND

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common, serious complication of CAR T-cell therapy for blood cancers. This study evaluates the impact of baseline cognitive status and pre-existing neurological injury on the occurrence of ICANS.

METHODS

We conducted a prospective study of adult patients treated with CAR T-cell therapy for aggressive B-cell lymphoma at our centre between May 2020 and December 2023. All patients underwent neurological examination, cerebral MRI and cognitive assessment measured by the Montreal Cognitive Assessment (MoCA). We measured total metabolic tumour volume (TMTV), lactate dehydrogenase (LDH), albumin, ferritin and C-reactive protein (CRP) before CART cell infusion, and serum neurofilament light chain (NfL) levels. We evaluated the impact of these factors on ICANS occurrence using multivariate analysis.

RESULTS

Among the 156 adult patients treated with CAR T-cell therapy, 32.7% developed ICANS. The median MoCA score at baseline was 26 [IQR 24; 28]. There was no significant association between the onset of ICANS and baseline cognitive performance (p 0.57). MoCA scores did not differ by ICANS grade. Pre-existing neurological injury were not associated with increased ICANS risk. In multivariable analysis, the use of CD28 CAR T cells was the strongest predictor of ICANS (p = 0.007). Slightly elevated serum NfL levels at leukapheresis predicted ICANS (p = 0.046) supporting its role in predicting risk of neurotoxicity rather than pre-existing neurological disease.

CONCLUSIONS

Our results suggest that pre-existing cognitive impairment or neurological history do not increase the risk of ICANS.

摘要

背景

免疫效应细胞相关神经毒性综合征（ICANS）是血液系统恶性肿瘤CAR T细胞治疗常见的严重并发症。本研究评估基线认知状态和既往神经损伤对ICANS发生的影响。

方法

我们对2020年5月至2023年12月在本中心接受CAR T细胞治疗侵袭性B细胞淋巴瘤的成年患者进行了一项前瞻性研究。所有患者均接受神经学检查、脑部MRI以及通过蒙特利尔认知评估量表（MoCA）进行的认知评估。我们在CART细胞输注前测量了总代谢肿瘤体积（TMTV）、乳酸脱氢酶（LDH）、白蛋白、铁蛋白和C反应蛋白（CRP），以及血清神经丝轻链（NfL）水平。我们使用多变量分析评估这些因素对ICANS发生的影响。

结果

在156例接受CAR T细胞治疗的成年患者中，32.7%发生了ICANS。基线时MoCA评分的中位数为26[四分位间距24；28]。ICANS的发生与基线认知表现之间无显著关联（p = 0.57）。MoCA评分在不同ICANS分级之间无差异。既往神经损伤与ICANS风险增加无关。在多变量分析中，使用CD28 CAR T细胞是ICANS最强的预测因素（p = 0.007）。白细胞分离时血清NfL水平略有升高可预测ICANS（p = 0.046），这支持其在预测神经毒性风险而非既往神经疾病方面的作用。