1. Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis.
- Author
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Guha, Avirup, Addison, Daniel, Jain, Prantesh, Gutierrez, Jahir M., Ghosh, Arjun, Roddie, Claire, de Lima, Marcos, Al-Kindi, Sadeer, and Oliveira, Guilherme H.
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CHIMERIC antigen receptors , *CARDIOVASCULAR diseases , *CD19 antigen , *CELLULAR therapy , *CYTOKINE release syndrome , *LYMPHOBLASTIC leukemia , *RITUXIMAB - Abstract
• FDA Adverse Events Reporting System data show 20% of chimeric antigen receptor T cell therapy adverse events were cardiovascular adverse events (CVEs). • CVEs had all-cause mortality of 30%. • Arrhythmias were the most frequent CVEs. • Neurotoxicity/immune effector cell-associated neurotoxicity syndrome clustered with CVEs and cytokine release syndrome 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. Image, graphical abstract [ABSTRACT FROM AUTHOR]
- Published
- 2020
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