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CAR-T 细胞治疗后非 ICANS 神经系统并发症:来自 EBMT 实践协调与指南委员会的建议

英文原题:Non-ICANS neurological complications after CAR T-cell therapies: recommendations from the EBMT Practice Harmonisation and Guidelines Committee.

PubMed 2025/04/01(内容时间) Lancet Oncol Q1 · IF 33.7(JCR 2025)

研究概要

神经系统并发症是接受嵌合抗原受体(CAR)T 细胞治疗的患者的重要关注点。

中文摘要

接受嵌合抗原受体(CAR)T 细胞治疗患者的神经系统并发症是重要关注事项。现有共识指南为免疫效应细胞相关神经毒性综合征(ICANS)的管理提供依据,但这些指南以早期 CD19 靶向 CAR-T 治疗 B 细胞恶性肿瘤的临床经验为基础。相比之下,对于其他非经典神经系统并发症,目前尚无已发表的最佳实践建议;这类并发症在 CAR-T 输注后较常发生,并可引起具有临床意义的神经毒性。随着 CAR-T 靶点增多(例如 B 细胞成熟抗原[BCMA])、疗法可及性扩大、临床开发的新适应证出现(包括 CNS 实体瘤)以及长期随访开展,这些非经典神经毒性并发症可能更常见。本综述由欧洲血液和骨髓移植学会(EBMT)实践协调与指南委员会撰写,对已获批 CD19 和 BCMA CAR-T 治疗后的相关神经系统并发症,以及实体瘤和血液系统恶性肿瘤 CAR-T 临床试验中新出现的神经毒性,提出管理建议。内容涵盖运动和神经认知毒性、脑神经麻痹、肿瘤炎症相关神经毒性、中风、脊髓病、周围神经病、格林-巴利综合征、氟达拉滨相关神经毒性,并为患者心理支持提供指导;不包括 CNS 感染。指南依据当前可用文献和专家意见制定,在可能情况下提出建议,并指出需进一步研究的领域,以建立改善患者照护的框架。

展开英文摘要原文

Neurological complications are an important concern in patients undergoing chimeric antigen receptor (CAR) T-cell therapy. Consensus guidelines inform the management of immune effector cell-associated neurotoxicity syndrome (ICANS). However, these guidelines are based on the early clinical experience with CD19 targeting CAR T cells in B-cell malignancies. In contrast, there are so far no published best practice recommendations on the current management of other non-classical neurological complications, which frequently develop after CAR T-cell infusion and cause clinically significant neurotoxicity. These non-classical neurological complications could be more prevalent because of additional CAR T-cell targets (eg, B cell maturation antigen [BCMA]), widened access, new indications in clinical development (including solid tumours in the CNS), and long-term follow-up. In this Review, the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonisation and Guidelines Committee provides recommendations on the management of CAR T-cell associated neurological complications that occur after treatment with the licensed CD19 and BCMA CAR T cells, as well as neurological toxicities that are emerging with CAR T cells in clinical trials for solid and haematological cancers. We address movement and neurocognitive toxicity, cranial nerve palsies, tumour inflammation-associated neurotoxicity, stroke, myelopathy, peripheral neuropathy, Guillain-Barr syndrome, fludarabine-associated neurotoxicity, and provide guidance on the psychological support for patients. CNS infections were excluded. The guidelines were developed based on the currently available literature and expert opinion. Recommendations are provided when possible, and areas for further research are highlighted to provide a framework to improve patient care.

论文信息

作者
Graham CE、Velasco R、Alarcon Tomas A、Stewart OP、Dachy G、Del Bufalo F、Doglio M、Henter JI
单位
Transplant Complications Working Party, EBMT, Paris, France; School of Cancer and Pharmaceutical Sciences, King's College London, London, UK; Department of Haematology, King's College Hospital NHS Foundation Trust, London, UK. Electronic address: charlotte.2.graham@kcl.ac.uk.France
文献类型
综述
期刊
The Lancet. Oncology2025 Apr
原文标识
PubMed 40179916 · DOI 10.1016/S1470-2045(24)00715-0