Wang Xin, He Xiaoyuan, Zhang Tao, Liu Jile, Zhao Mingfeng
First Center Clinical College, Tianjin Medical University, Tianjin, 300070, China.
Department of Hematology, Tianjin Thrombosis and Hemostasis Institute, Tianjin First Central Hospital, No.2 Baoshan West Road, Xiqing District, Tianjin, 300192, China.
Ann Hematol. 2025 Jun 19. doi: 10.1007/s00277-025-06467-y.
Nowadays, chimeric antigen receptor (CAR) -T cell therapy has shown significant efficacy in treating hematological tumors, with an obvious increase in patient survival rates. However, with the widespread application of CAR-T, the incidence of CAR-T related adverse events has gradually increased, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), and hemophagocytic lymphohistiocytosis (HLH). These complications may be life-threatening, so early diagnosis and intervention treatment are crucial for the prognosis of patients. In this review, we first comprehensively summarize the latest insights into the pathogenesis and clinical manifestations of CRS, ICANS, and HLH after CAR-T, with a focus on elaborating on the specific mechanisms and related pathways of the inflammatory storm caused by a large number of cytokines after CAR-T. We also discussed the established prevention and management strategies for the three complications mentioned above, and demonstrated the effectiveness of the treatment by introducing the therapeutic effects of various treatment methods in current clinical or preclinical trials. In addition, we provide a prospective perspective on the measures and modifications currently being studied to mitigate the toxicity associated with CAR-T cell therapy.
如今,嵌合抗原受体(CAR)-T细胞疗法在治疗血液肿瘤方面已显示出显著疗效,患者生存率明显提高。然而,随着CAR-T的广泛应用,CAR-T相关不良事件的发生率逐渐上升,包括细胞因子释放综合征(CRS)、免疫效应细胞相关神经毒性综合征(ICANS)和噬血细胞性淋巴组织细胞增生症(HLH)。这些并发症可能危及生命,因此早期诊断和干预治疗对患者的预后至关重要。在本综述中,我们首先全面总结了CAR-T后CRS、ICANS和HLH发病机制及临床表现的最新见解,重点阐述了CAR-T后大量细胞因子引发炎症风暴的具体机制及相关途径。我们还讨论了上述三种并发症已确立的预防和管理策略,并通过介绍当前临床或临床前试验中各种治疗方法的治疗效果来证明治疗的有效性。此外,我们对目前正在研究的减轻CAR-T细胞疗法相关毒性的措施和改进方法提供了前瞻性展望。
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