CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
接受嵌合抗原受体修饰 T 细胞治疗的大 B 细胞淋巴瘤患者中免疫效应细胞相关神经毒性综合征后的持续性神经系统症状
英文原题：Prolonged Neurologic Symptoms Following Immune Effector Cell-Associated Neurotoxicity Syndrome in Patients With Large B-cell Lymphoma Treated With Chimeric Antigen Receptor-Modified T Cell Therapy.
查看英文原题
Prolonged Neurologic Symptoms Following Immune Effector Cell-Associated Neurotoxicity Syndrome in Patients With Large B-cell Lymphoma Treated With Chimeric Antigen Receptor-Modified T Cell Therapy.
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中文摘要
虽然免疫效应细胞相关神经毒性综合征（ICANS）是嵌合抗原受体修饰T细胞（CAR-T）治疗相关的明确不良反应，但部分患者会出现迁延性神经系统症状。很少有研究探讨出现此类症状患者的特征和结局。
本研究的目的是在单中心接受商业化CAR-T 治疗的大B细胞淋巴瘤（LBCL）患者队列中，对发生ICANS的患者进行分析，并比较随后出现与未出现迁延性神经系统症状患者的特征和结局。
我们回顾性分析了在本机构接受CAR-T 治疗并发生ICANS的LBCL患者队列。迁延性神经系统症状定义为持续超过四周的症状。278例接受商业化CAR-T 治疗的LBCL患者中，33例（12%）发生了ICANS。9例患者（27%）在ICANS后出现迁延性神经系统症状，其中8例为ICANS 3级（高级别），1例为ICANS <3级（低级别）。这些患者出现了一系列症状，包括短期记忆困难、长期记忆困难、失语症和震颤。发生高级别ICANS的患者中迁延性神经系统症状的发生率高于低级别ICANS患者（42.1% vs. 7.1%，P = .049）。
然而，未发现其他治疗前特征或治疗后结局与ICANS后迁延性神经系统症状的发生相关。总之，在我们机构接受CAR-T 治疗的LBCL患者中，近一半发生高级别ICANS的患者出现了迁延性神经系统症状；然而，治疗前特征和治疗后结局均无法预测这一临床状况。需要进一步研究以识别接受CAR-T 治疗后存在迁延性神经系统症状风险的患者，并制定该毒性的评估和治疗策略。
展开英文摘要原文
While immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-defined adverse effect associated with chimeric antigen receptor-modified T cell (CAR-T) therapy, some patients develop prolonged neurologic symptoms. Few studies have examined characteristics and outcomes of patients who develop such symptoms.
The objective of this study was to provide an analysis of patients who developed ICANS in a single-center cohort of patients with large B-cell lymphoma (LBCL) who received commercial CAR-T and compare characteristics and outcomes between patients with vs. without subsequent prolonged neurologic symptoms.
We examined a retrospective cohort of patients with LBCL treated with CAR-T at our institution who developed ICANS. Prolonged neurologic symptoms were defined as those lasting longer than four weeks. Thirty three of 278 (12%) LBCL patients treated with commercial CAR-T experienced ICANS. Nine patients (27%) experienced prolonged neurologic symptoms following ICANS, eight with ICANS grade 3 (high-grade) and one with ICANS grade <3 (low-grade).
There were a range of symptoms experienced by these patients including difficulties with short-term memory, difficulties with long-term memory, aphasia, and tremors. The incidence of prolonged neurologic symptoms was greater in patients experiencing high-grade as compared to low-grade ICANS (42. 1% vs. 7. 1%, P = . 049).
However, no other pre-treatment characteristics or post-treatment outcomes were associated with development of prolonged neurologic symptoms following ICANS. In summary, nearly half of all patients with LBCL treated with CAR-T at our institution who developed high-grade ICANS experienced prolonged neurologic symptoms; however, pretreatment characteristics and post-treatment outcomes were not predictive of this clinical condition.
Further work is needed to identify patients treated with CAR-T at risk for experiencing prolonged neurologic symptoms and developing strategies for evaluation and treatment of this toxicity.
论文信息
- 作者
- Maillie L、Nasta SD、Svoboda J、Barta SK、Chong EA、Garfall AL、Gill SI、Porter DL
- 单位
- Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: lukemaillie18@gmail.com.United States
- 期刊
- Transplantation and cellular therapy2025 Apr
- 原文标识
- PubMed 39848443 · DOI 10.1016/j.jtct.2025.01.884