Atrial arrhythmias following CAR-chimeric antigen receptor T-cell therapy: Incidence, risk factors and biomarker profile Journal Article
| Authors: | Shouval, R.; Goldman, A.; Flynn, J. R.; El-Moghraby, A.; Rehman, M.; Devlin, S. M.; Corona, M.; Landego, I.; Lin, R. J.; Scordo, M.; Raj, S. S.; Giralt, S. A.; Palomba, M. L.; Dahi, P. B.; Walji, M.; Salles, G.; Nath, K.; Geyer, M. B.; Park, J. H.; Fein, J. A.; Kosmidou, I.; Shah, G. L.; Liu, J. E.; Perales, M. A.; Mahmood, S. S. |
| Article Title: | Atrial arrhythmias following CAR-chimeric antigen receptor T-cell therapy: Incidence, risk factors and biomarker profile |
| Abstract: | Recent reports have raised concerns about the association of chimeric antigen receptor T cell (CAR-T) with non-negligible cardiotoxicity, particularly atrial arrhythmias. First, we conducted a pharmacovigilance study to assess the reporting of atrial arrhythmias following CD19-directed CAR-T. Subsequently, to determine the incidence, risk factors and outcomes of atrial arrhythmias post-CAR-T, we compiled a retrospective single-centre cohort of non-Hodgkin lymphoma patients. Only commercial CAR-T products were considered. Atrial arrhythmias were nearly fourfold more likely to be reported after CAR-T therapy compared to all other cancer patients in the FAERS (adjusted ROR = 3.76 [95% CI 2.67–5.29]). Of the 236 patients in our institutional cohort, 23 (10%) developed atrial arrhythmias post-CAR-T, including 12 de novo arrhythmias, with most (83%) requiring medical intervention. Atrial arrhythmias frequently co-occurred with cytokine release syndrome and were associated with higher post-CAR-T infusion peak levels of IL-10, TNF-alpha and LDH, and lower trough levels of fibrinogen. In a multivariable analysis, risk factors for atrial arrhythmia were history of atrial arrhythmia (OR = 6.80 [2.39–19.6]) and using CAR-T product with a CD28-costimulatory domain (OR = 5.17 [1.72–18.6]). Atrial arrhythmias following CD19-CAR-T therapy are prevalent and associated with elevated inflammatory biomarkers, a history of atrial arrhythmia and the use of a CAR-T product with a CD28 costimulatory domain. © 2024 British Society for Haematology and John Wiley & Sons Ltd. |
| Keywords: | immunotherapy; cardiotoxicity; atrial arrhythmias; cardio-oncology; chimeric antigen receptor t cell |
| Journal Title: | British Journal of Haematology |
| Volume: | 205 |
| Issue: | 3 |
| ISSN: | 0007-1048 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2024-09-01 |
| Start Page: | 978 |
| End Page: | 989 |
| Language: | English |
| DOI: | 10.1111/bjh.19497 |
| PUBMED: | 38735683 |
| PROVIDER: | scopus |
| PMCID: | PMC11499037 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Roni Shouval -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work