Atrial arrhythmias following CAR-chimeric antigen receptor T-cell therapy: Incidence, risk factors and biomarker profile

Roni Shouval, Adam Goldman, Jessica R. Flynn, Ahmed El-Moghraby, Mahin Rehman, Sean M. Devlin, Magdalena Corona, Ivan Landego, Richard J Lin, Michael Scordo, Sandeep S. Raj, Sergio A. Giralt, M.  Lia Palomba, Parastoo B. Dahi, Moneeza Walji, Gilles Salles, Karthik Nath, Mark B. Geyer, Jae H. Park, Joshua A. FeinIoanna Kosmidou, Gunjan L. Shah, Jennifer E. Liu, Miguel Angel Perales, Syed S. Mahmood

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalBritish Journal of Haematology
Early online date12 May 2024
DOIs
StateE-pub ahead of print - 12 May 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024 British Society for Haematology and John Wiley & Sons Ltd.

Keywords

  • atrial arrhythmias
  • cardio-oncology
  • cardiotoxicity
  • chimeric antigen receptor T cell
  • immunotherapy

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