与嵌合抗原受体T细胞治疗相关的心血管事件:横断面FDA不良事件报告系统分析

Avirup Guha , Daniel Addison , Prantesh Jain , Jahir M. Gutierrez , Arjun Ghosh , Claire Roddie , Marcos de Lima , Sadeer Al-Kindi , Guilherme H. Oliveira
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引用次数: 33

摘要

嵌合抗原受体(CAR) T细胞疗法在美国被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。与car - t相关的多种心血管不良事件(CVEs)已在小型研究中观察到,但没有大规模的研究存在。利用美国食品和药物管理局(FDA)不良事件报告系统(FAERS),我们确定了2017年至2019年与CAR-T治疗(tisagenlecleucel和axicabtagene ciloleucel)相关的所有报告的不良事件(ae)。年龄和性别缺失的报告被排除在外。cve分为心律失常、心力衰竭(HF)、心肌梗死(MI)和其他cve。采用逻辑回归和分层聚类来确定与cve相关的因素。共观察到996例报告的ae(39.1%与tisagenlecleel相关,60%与axicabtagene ciloleel相关)。在所有经历ae的患者中,中位年龄为54岁(四分位数范围为21至65岁);38.9%为女性。向FDA报告的所有ae中,19.7%(196例)为cve。最常见的cve是心律失常(77.6%),其次是HF(14.3%)和MI(0.5%)。校正分析显示,CVE患者与神经毒性呈正相关(优势比为1.76;95%置信区间为1.20 ~ 2.60;P = 04)。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,与它们聚集在一起(Jaccard相似度:73.1)。总体死亡率为21.1%,但报告cve的死亡率为30.1%。在FAERS中,CAR-T合并cve的报道与高死亡率相关。CRS或神经毒性的发生应引起对心血管事件的警惕。
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Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis

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.

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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
1061
审稿时长
3-6 weeks
期刊介绍: Biology of Blood and Marrow Transplantation publishes original research reports, reviews, editorials, commentaries, letters to the editor, and hypotheses and is the official publication of the American Society for Transplantation and Cellular Therapy. The journal focuses on current technology and knowledge in the interdisciplinary field of hematopoetic stem cell transplantation.
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