Adverse cardiovascular and pulmonary events associated with chimeric antigen receptor T-cell therapy Journal Article
| Authors: | Goldman, A.; Maor, E.; Bomze, D.; Liu, J. E.; Herrmann, J.; Fein, J.; Steingart, R. M.; Mahmood, S. S.; Schaffer, W. L.; Perales, M. A.; Shouval, R. |
| Article Title: | Adverse cardiovascular and pulmonary events associated with chimeric antigen receptor T-cell therapy |
| Abstract: | Background: Pivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs). Objectives: This study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy. Methods: In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. The authors evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025 >0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR). Results: The authors identified CAR-T reports of 2,657 patients, including 546 CPAEs (20.5%). CPAEs overlapped with cytokine release syndrome in 68.3% (373 of 546) of the reports. Compared with the full database, CAR-T was associated with overreporting of tachyarrhythmias (n = 74 [2.8%], adj.ROR = 2.78 [95% CI: 2.21-3.51]), cardiomyopathy (n = 69 [2.6%], adj.ROR = 3.51 [2.42-5.09]), pleural disorders (n = 46 [1.7%], adj.ROR = 3.91 [2.92-5.23]), and pericardial diseases (n = 11 [0.4%], adj.ROR = 2.26 [1.25-4.09], all IC025 >0). Venous thromboembolic events (VTEs) were associated only with axicabtagene-ciloleucel therapy (n = 28 [1.6%], adj.ROR = 1.80 [1.24-2.62], IC025 >0). Atrial fibrillation (n = 55) was the leading tachyarrhythmia, followed by ventricular arrhythmias (n = 14). Tachyarrhythmias and VTEs were reported more often following axicabtagene-ciloleucel than tisagenlecleucel in an age- and sex-adjusted model (adj.ROR = 1.82 [1.04-3.18] and adj.ROR = 2.86 [1.18-6.93], respectively). Finally, the fatality rate of CPAEs was 30.9%. Conclusions: In this largest post-marketing study to date, the authors identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. These findings should be considered in the multidisciplinary assessment for and monitoring of CAR-T therapy recipients. © 2021 American College of Cardiology Foundation |
| Keywords: | venous thromboembolism; cardio-oncology; cardiac arrhythmias; pharmacovigilance; chimeric antigen receptor t cell; cardiovascular adverse events |
| Journal Title: | Journal of the American College of Cardiology |
| Volume: | 78 |
| Issue: | 18 |
| ISSN: | 0735-1097 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2021-11-02 |
| Start Page: | 1800 |
| End Page: | 1813 |
| Language: | English |
| DOI: | 10.1016/j.jacc.2021.08.044 |
| PROVIDER: | scopus |
| PMCID: | PMC8562317 |
| PUBMED: | 34711339 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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