Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Department of Medicine, Weill Cornell Medical College, New York, New York, USA.
Br J Haematol. 2024 Sep;205(3):978-989. doi: 10.1111/bjh.19497. Epub 2024 May 12.
Recent reports have raised concerns about the association of chimeric antigen receptor T cell (CAR-T) with non-negligible cardiotoxicity, particularly atrial arrhythmias. First, we conducted a pharmacovigilance study to assess the reporting of atrial arrhythmias following CD19-directed CAR-T. Subsequently, to determine the incidence, risk factors and outcomes of atrial arrhythmias post-CAR-T, we compiled a retrospective single-centre cohort of non-Hodgkin lymphoma patients. Only commercial CAR-T products were considered. Atrial arrhythmias were nearly fourfold more likely to be reported after CAR-T therapy compared to all other cancer patients in the FAERS (adjusted ROR = 3.76 [95% CI 2.67-5.29]). Of the 236 patients in our institutional cohort, 23 (10%) developed atrial arrhythmias post-CAR-T, including 12 de novo arrhythmias, with most (83%) requiring medical intervention. Atrial arrhythmias frequently co-occurred with cytokine release syndrome and were associated with higher post-CAR-T infusion peak levels of IL-10, TNF-alpha and LDH, and lower trough levels of fibrinogen. In a multivariable analysis, risk factors for atrial arrhythmia were history of atrial arrhythmia (OR = 6.80 [2.39-19.6]) and using CAR-T product with a CD28-costimulatory domain (OR = 5.17 [1.72-18.6]). Atrial arrhythmias following CD19-CAR-T therapy are prevalent and associated with elevated inflammatory biomarkers, a history of atrial arrhythmia and the use of a CAR-T product with a CD28 costimulatory domain.
最近的报告引起了人们对嵌合抗原受体 T 细胞（CAR-T）与不可忽视的心脏毒性相关的关注，尤其是心房性心律失常。首先，我们进行了一项药物警戒研究，以评估 CD19 定向 CAR-T 后心房性心律失常的报告情况。随后，为了确定 CAR-T 后心房性心律失常的发生率、风险因素和结局，我们汇编了一个回顾性的单中心非霍奇金淋巴瘤患者队列。仅考虑商业 CAR-T 产品。与所有其他癌症患者相比，CAR-T 治疗后心房性心律失常的报告率几乎高出四倍（调整后的 ROR=3.76[95%CI 2.67-5.29]）。在我们的机构队列中，236 名患者中有 23 名（10%）在 CAR-T 后出现心房性心律失常，包括 12 例新发心律失常，其中大多数（83%）需要医疗干预。心房性心律失常常与细胞因子释放综合征同时发生，并与 CAR-T 输注后 IL-10、TNF-α和 LDH 峰值水平升高以及纤维蛋白原水平降低相关。在多变量分析中，心房性心律失常的危险因素包括心房性心律失常史（OR=6.80[2.39-19.6]）和使用具有 CD28 共刺激结构域的 CAR-T 产品（OR=5.17[1.72-18.6]）。CD19-CAR-T 治疗后心房性心律失常很常见，与炎症生物标志物升高、心房性心律失常史和使用具有 CD28 共刺激结构域的 CAR-T 产品相关。
