Bach Franziska, Grans-Seibel Judit, Garcia-Borrega Jorge, Böll Boris
Klinik I für Innere Medizin, Hämatologie-Onkologie und Internistische Intensivmedizin, Uniklinik Köln, Kerpener Straße 62, 50937, Köln, Deutschland.
Inn Med (Heidelb). 2025 Jul 8. doi: 10.1007/s00108-025-01944-y.
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.
嵌合抗原受体（CAR）T细胞疗法显著改善了血液系统肿瘤患者的治疗结局，六种CAR T细胞产品的获批使得其常规使用日益增加；然而，CAR T细胞疗法会引发特定的、有时甚至是严重的副作用，本文将对此进行总结。细胞因子释放综合征（CRS）是CAR T细胞激活后细胞因子大量释放引发的常见全身性炎症反应。症状从轻度发热到多器官功能衰竭不等。根据严重程度，逐步使用托珠单抗和皮质类固醇进行治疗，近期数据支持使用阿那白滞素。其他靶向治疗药物似乎也很有前景。与CRS相比，免疫效应细胞相关噬血细胞性淋巴组织细胞增生症样综合征（IEC-HS）较为罕见，但危及生命，其特征为铁蛋白水平升高、血细胞减少和器官功能衰竭。治疗包括使用阿那白滞素、地塞米松和其他挽救性药物，因此识别该并发症至关重要。免疫效应细胞相关神经毒性综合征（ICANS）相对较为常见，表现为意识混乱、言语障碍或癫痫发作等症状。治疗取决于严重程度，通常包括使用皮质类固醇、阿那白滞素和其他免疫抑制剂。除了ICANS，还可能出现一组异质性更强的罕见神经并发症，这些并发症往往难以治疗且尚未完全明确。伴有长期血细胞减少的血液毒性（免疫效应细胞相关血液毒性，ICAHT）是一种日益被认识到的并发症，在淋巴细胞清除前可使用一个简单评分来评估其风险。长期血细胞减少会大幅增加感染风险，这也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。总之，自首次获批以来，通过对病理生理学的更好理解、风险因素的识别，尤其是早期干预策略，CAR T细胞相关副作用的管理已得到显著改善。
