CAR - t细胞治疗后的非icans神经系统并发症:来自EBMT实践协调和指南委员会的建议

Charlotte E Graham, Roser Velasco, Ana Alarcon Tomas, Orla P Stewart, Guillaume Dachy, Francesca del Bufalo, Matteo Doglio, Jan-Inge Henter, Guillermo Ortí, Zinaida Peric, Claire Roddie, Niels W C J van de Donk, Matthew J Frigault, Annalisa Ruggeri, Francesco Onida, Isabel Sánchez-Ortega, Ibrahim Yakoub-Agha, Olaf Penack
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引用次数: 0

摘要

神经系统并发症是患者接受嵌合抗原受体(CAR) t细胞治疗的一个重要问题。共识指南告知免疫效应细胞相关神经毒性综合征(ICANS)的管理。然而,这些指南是基于CD19靶向CAR - T细胞治疗b细胞恶性肿瘤的早期临床经验。相比之下,到目前为止,还没有发表的关于其他非经典神经系统并发症的最佳实践建议,这些并发症经常在CAR - t细胞输注后发生,并引起临床显着的神经毒性。由于CAR -t细胞靶点(如B细胞成熟抗原[BCMA])的增加、治疗途径的拓宽、临床发展中的新适应症(包括中枢神经系统的实体肿瘤)和长期随访,这些非经典神经系统并发症可能更为普遍。在本综述中,欧洲血液和骨髓移植学会(EBMT)实践协调和指南委员会提供了CAR - T细胞相关神经系统并发症的管理建议,这些并发症发生在使用CD19和BCMA CAR - T细胞治疗后,以及CAR - T细胞在实体和血液系统癌症的临床试验中出现的神经系统毒性。我们处理运动和神经认知毒性、脑神经麻痹、肿瘤炎症相关的神经毒性、中风、脊髓病、周围神经病变、格林-巴罗综合征、氟达拉滨相关的神经毒性,并为患者提供心理支持指导。排除中枢神经系统感染。这些准则是根据现有文献和专家意见制定的。在可能的情况下提供建议,并强调进一步研究的领域,以提供改善患者护理的框架。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Non-ICANS neurological complications after CAR T-cell therapies: recommendations from the EBMT Practice Harmonisation and Guidelines Committee
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–Barré 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.
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