[Management of side effects of CAR T cells].

Franziska Bach, Judit Grans-Seibel, Jorge Garcia-Borrega, Boris Böll
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Abstract

Chimeric antigen receptor (CAR) T cell therapy has significantly improved outcomes for patients with hematological neoplasms and the approval of six CAR T cell products has led to increasing routine use; however, CAR T cell therapy is associated with specific and sometimes severe side effects, which are summarized in this article. Cytokine release syndrome (CRS) is a frequent systemic inflammatory reaction triggered by the massive release of cytokines after CAR T cell activation. The symptoms range from mild fever to multiorgan failure. The management is stepwise using tocilizumab and corticosteroids depending on the severity, with recent data supporting the use of anakinra. Further targeted therapeutic agents appear to be promising. The immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) is rare compared to CRS but life-threatening and is characterized by high ferritin levels, cytopenia and organ failure. Treatment includes anakinra, dexamethasone and other salvage medications, whereby recognition of the complication is essential. Immune effector cell-associated neurotoxicity syndrome (ICANS) is comparatively frequent, presenting with symptoms such as confusion, speech disturbances or seizures. The treatment depends on the severity and usually involves corticosteroids, anakinra and other immunosuppressants. Besides ICANS, a heterogeneous group of rarer neurological complications can also occur, which are often difficult to treat and not yet fully understood. Hematotoxicity with prolonged cytopenia (immune effector cell-associated hematotoxicity, ICAHT) is an increasingly recognized complication and its risk can be estimated before lymphocyte depletion using a simple score. Prolonged cytopenia substantially increases the risk of infections and explains why infections are the most frequent non-disease-related cause of death after CAR T cell treatment. In summary, since the first approval the management of CAR T cell-related side effects has markedly improved through a better understanding of the pathophysiology, identification of risk factors and especially early intervention strategies.

【CAR - T细胞副作用的处理】。
嵌合抗原受体(CAR) T细胞疗法显著改善了血液肿瘤患者的预后,六种CAR T细胞产品的批准导致常规使用的增加;然而,CAR - T细胞疗法具有特异性,有时甚至是严重的副作用,本文对此进行了总结。细胞因子释放综合征(CRS)是一种常见的全身炎症反应,由CAR - T细胞激活后大量释放细胞因子引起。症状从轻度发烧到多器官衰竭。治疗方法是根据病情的严重程度逐步使用托珠单抗和皮质类固醇,最近的数据支持使用阿那真纳。进一步的靶向治疗药物似乎很有希望。与CRS相比,免疫效应细胞相关的噬血细胞淋巴组织细胞病样综合征(IEC-HS)比较罕见,但危及生命,其特征是高铁蛋白水平、细胞减少和器官衰竭。治疗包括阿那白、地塞米松和其他抢救性药物,因此识别并发症是必要的。免疫效应细胞相关神经毒性综合征(ICANS)比较常见,表现为精神错乱、言语障碍或癫痫发作等症状。治疗取决于病情的严重程度,通常包括皮质类固醇、阿那白和其他免疫抑制剂。除了ICANS之外,还可能发生多种罕见的神经系统并发症,这些并发症通常难以治疗,而且尚未完全了解。长期细胞减少的血液毒性(免疫效应细胞相关的血液毒性,ICAHT)是一种越来越被认可的并发症,其风险可以在淋巴细胞消耗之前使用简单的评分来估计。长期的细胞减少大大增加了感染的风险,并解释了为什么感染是CAR - T细胞治疗后最常见的非疾病相关死亡原因。综上所述,自首次批准以来,通过更好地了解病理生理学,识别风险因素,特别是早期干预策略,CAR - T细胞相关副作用的管理有了显着改善。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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