| アブストラクト | 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. |
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| ジャーナル名 | Journal of the American College of Cardiology |
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| 投稿日 | 2021/10/30 |
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| 投稿者 | Goldman, Adam; Maor, Elad; Bomze, David; Liu, Jennifer E; Herrmann, Joerg; Fein, Joshua; Steingart, Richard M; Mahmood, Syed S; Schaffer, Wendy L; Perales, Miguel-Angel; Shouval, Roni |
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| 組織名 | Leviev Heart Center, Chaim Sheba Medical Center, Ramat Gan, Israel; School of;Medicine, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.;School of Medicine, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv,;Israel.;Cardiology Service, Department of Medicine, Memorial Sloan Kettering Cancer;Center, New York, New York, USA; Department of Medicine, Weill Cornell Medical;College, New York, New York, USA.;Department of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota, USA.;Department of Internal Medicine, UCONN Health, Farmington, Connecticut, USA.;Cardiology Division, New York-Presbyterian Hospital, Weill Cornell Medical;Center, New York, New York, USA.;Department of Medicine, Weill Cornell Medical College, New York, New York, USA;;Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer;Center, New York, New York, USA. Electronic address: shouvalr@mskcc.org. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/34711339/ |
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