Harrington Heart and Vascular Institute, University Hospitals, Case Western Reserve University, Cleveland, Ohio.
Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio; Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio.
Biol Blood Marrow Transplant. 2020 Dec;26(12):2211-2216. doi: 10.1016/j.bbmt.2020.08.036. Epub 2020 Sep 20.
Chimeric antigen receptor (CAR) T cell therapy is approved in the United States for the treatment of acute lymphocytic leukemia and aggressive B cell lymphomas. Multiple cardiovascular adverse events (CVEs) associated with CAR-Ts have been observed in small studies, but no large-scale studies exist. Leveraging the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), we identified all reported adverse events (AEs) associated with CAR-T therapy (tisagenlecleucel and axicabtagene ciloleucel) from 2017 to 2019. Reports with missing age and sex were excluded. CVEs were classified into arrhythmias, heart failure (HF), myocardial infarction (MI), and other CVEs. Logistic regression and hierarchical clustering were used to identify factors associated with CVEs. A total of 996 reported AEs were observed (39.1% associated with tisagenlecleucel and 60% with axicabtagene ciloleucel). Of all patients experiencing AEs, the median age was 54 (interquartile range, 21 to 65) years; 38.9% were females. In total, 19.7% (196) of all AEs reported to the FDA were CVEs. The most common CVEs were arrhythmia (77.6%), followed by HF (14.3%) and MI (0.5%). In adjusted analysis a positive association was observed between those presenting with CVE with neurotoxicity (odds ratio, 1.76; 95% confidence interval, 1.20 to 2.60; P = .004). Additionally, when both CVE and cytokine release syndrome (CRS) are present, neurotoxicity is the most common noncardiac AE, which clusters with them (Jaccard similarity: 73.1). The mortality rate was 21.1% overall but 30.1% for those reporting CVEs. In FAERS, reported CVEs with CAR-T are associated with high reported mortality. The development of either CRS or neurotoxicity should prompt vigilance for cardiovascular events.
嵌合抗原受体 (CAR) T 细胞疗法已获美国批准，用于治疗急性淋巴细胞白血病和侵袭性 B 细胞淋巴瘤。在小型研究中观察到与 CAR-T 相关的多种心血管不良事件 (CVE)，但尚无大规模研究。利用美国食品和药物管理局 (FDA) 不良事件报告系统 (FAERS)，我们从 2017 年至 2019 年确定了与 CAR-T 治疗相关的所有报告的不良事件 (AE)（tisagenlecleucel 和 axicabtagene ciloleucel）。排除了年龄和性别缺失的报告。CVE 分为心律失常、心力衰竭 (HF)、心肌梗死 (MI) 和其他 CVE。使用逻辑回归和层次聚类来识别与 CVE 相关的因素。共观察到 996 例报告的 AE（39.1%与 tisagenlecleucel 相关，60%与 axicabtagene ciloleucel 相关）。在所有发生 AE 的患者中，中位年龄为 54 岁（四分位距，21 至 65 岁）；38.9%为女性。共有 19.7%（196）向 FDA 报告的所有 AE 为 CVE。最常见的 CVE 是心律失常 (77.6%)，其次是 HF (14.3%)和 MI (0.5%)。在调整分析中，与 CVE 相关的患者与神经毒性之间存在正相关关系（比值比，1.76；95%置信区间，1.20 至 2.60；P=0.004）。此外，当 CVE 和细胞因子释放综合征 (CRS) 同时存在时，神经毒性是最常见的非心脏 AE，与它们聚类（Jaccard 相似性：73.1）。总体死亡率为 21.1%，但报告 CVE 的患者死亡率为 30.1%。在 FAERS 中，与 CAR-T 相关的报告 CVE 与高报告死亡率相关。CRS 或神经毒性的发展应警惕心血管事件。
