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[现代免疫疗法与紧急情况:嵌合抗原受体T细胞疗法和双特异性T细胞衔接器的毒性、管理及其在重症医学中的相关性]

[Modern immunotherapy and emergency situations : Toxicities of CAR T-cell therapies and BiTEs, their management, and their relevance in intensive care medicine].

作者信息

Grans-Siebel Judit, Garcia Borrega Jorge, Böll Boris, Bach Franziska

机构信息

Klinik I für Innere Medizin - Hämatologie/Onkologie, Internistische Intensivmedizin, Centrum für Integrierte Onkologie Aachen Bonn Köln Düsseldorf (CIO), Universitätsklinikum Köln, Kerpener Straße 62, 50937, Köln, Deutschland.

出版信息

Med Klin Intensivmed Notfmed. 2025 Sep 2. doi: 10.1007/s00063-025-01316-2.

DOI:10.1007/s00063-025-01316-2
PMID:40892214
Abstract

Novel immunotherapies such as chimeric antigen receptor T‑cell therapy (CAR T‑cell therapy) and bispecific T‑cell engagers (BiTEs) have transformed the treatment of hematologic malignancies in recent years. Despite their high efficacy, they pose considerable risks, particularly for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Both typically occur within the first 2 weeks after therapy and may require admission to an intensive care unit (ICU). Other relevant side effects include persistent cytopenias, hypogammaglobulinemia, and increased susceptibility to infections. These long-term complications are gaining importance and require structured follow-up strategies. Up to 35% of patients undergoing CAR T‑cell therapy require intensive care, mostly due to CRS or ICANS. Nevertheless, the rates of organ support and ICU mortality remain comparatively low, indicating that these toxicities are, in principle, manageable. The severe toxicities of these novel therapies increasingly pose ethical challenges in intensive care. Decision-making frameworks such as the "ICU trial" model can provide valuable guidance. This article offers a comprehensive overview of acute and delayed side effects of immune-based therapies, their intensive care management, and current strategies for optimizing patient care.

摘要

近年来,嵌合抗原受体T细胞疗法(CAR T细胞疗法)和双特异性T细胞衔接器(BiTEs)等新型免疫疗法改变了血液系统恶性肿瘤的治疗方式。尽管它们疗效显著,但也带来了相当大的风险,尤其是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)。这两种情况通常在治疗后的前2周内出现,可能需要入住重症监护病房(ICU)。其他相关副作用包括持续性血细胞减少、低丙种球蛋白血症以及感染易感性增加。这些长期并发症日益受到重视,需要有结构化的随访策略。接受CAR T细胞疗法的患者中,高达35%需要重症监护,主要原因是CRS或ICANS。然而,器官支持率和ICU死亡率相对较低,这表明这些毒性原则上是可控的。这些新型疗法的严重毒性在重症监护中日益引发伦理挑战。“ICU试验”模型等决策框架可以提供有价值的指导。本文全面概述了基于免疫疗法的急性和延迟副作用、其重症监护管理以及当前优化患者护理的策略。

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Mechanisms and management of CAR T toxicity.嵌合抗原受体T细胞毒性的机制与管理
Front Oncol. 2024 May 21;14:1396490. doi: 10.3389/fonc.2024.1396490. eCollection 2024.
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Toxicities, intensive care management, and outcome of chimeric antigen receptor T cells in adults: an update.嵌合抗原受体 T 细胞在成人中的毒性、重症监护管理和结局:最新进展。
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Long-term outcomes of patients with large B-cell lymphoma treated with axicabtagene ciloleucel and prophylactic corticosteroids.接受 axi-cel 和预防性皮质类固醇治疗的大 B 细胞淋巴瘤患者的长期结果。
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