Penack Olaf, Koenecke Christian
Department for Hematology, Oncology and Tumorimmunology, Charité Universitätsmedizin Berlin, Campus Virchow Clinic, Augustenburger Platz, 113353 Berlin, Germany.
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Cancers (Basel). 2020 Nov 19;12(11):3445. doi: 10.3390/cancers12113445.
Clinical trials demonstrated that CD19+ chimeric antigen receptor (CAR) T-cells can be highly effective against a number of malignancies. However, the complete risk profile of CAR T-cells could not be defined in the initial trials. Currently, there is emerging evidence derived from post approval studies in CD19+ CAR T-cells demonstrating both short-term and medium-term effects, which were unknown at the time of regulatory approval. Here, we review the incidence and the current management of CD19+ CAR T-cell complications. We highlight frequently occurring events, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cardiotoxicity, pulmonary toxicity, metabolic complications, secondary macrophage-activation syndrome, and prolonged cytopenia. Furthermore, we present evidence supporting the hypothesis that CAR T-cell-mediated toxicities can involve any other organ system and we discuss the potential risk of long-term complications. Finally, we discuss recent pre-clinical and clinical data shedding new light on the pathophysiology of CAR T-cell-related complications.
临床试验表明，CD19+嵌合抗原受体（CAR）T细胞对多种恶性肿瘤可能具有高度疗效。然而，在最初的试验中无法确定CAR T细胞的完整风险概况。目前，来自CD19+ CAR T细胞批准后研究的新证据表明了短期和中期效应，而这些效应在监管批准时是未知的。在此，我们回顾CD19+ CAR T细胞并发症的发生率及当前的处理方法。我们重点介绍了常见的事件，如细胞因子释放综合征、免疫效应细胞相关神经毒性综合征、心脏毒性、肺毒性、代谢并发症、继发性巨噬细胞活化综合征和持续性血细胞减少。此外，我们提供证据支持CAR T细胞介导的毒性可能累及任何其他器官系统这一假说，并讨论长期并发症的潜在风险。最后，我们讨论了最近的临床前和临床数据，这些数据为CAR T细胞相关并发症的病理生理学提供了新的线索。
