Atrial arrhythmias following CAR-chimeric antigen receptor T-cell therapy: Incidence, risk factors and biomarker profile.
Roni ShouvalAdam GoldmanJessica R FlynnAhmed El-MoghrabyMahin RehmanSean M DevlinMagdalena CoronaIvan LandegoRichard J LinMichael ScordoSandeep S RajSergio A GiraltM Lia PalombaParastoo Bahrami DahiMoneeza WaljiGilles SallesKarthik NathMark B GeyerJae H ParkJoshua A FeinIoanna KosmidouGunjan L ShahJennifer E LiuMiguel-Ángel PeralesSyed S MahmoodPublished in: British journal of haematology (2024)
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.
Keyphrases
- atrial fibrillation
- catheter ablation
- left atrial
- risk factors
- congenital heart disease
- end stage renal disease
- chronic kidney disease
- randomized controlled trial
- newly diagnosed
- rheumatoid arthritis
- healthcare
- low dose
- emergency department
- type diabetes
- heart failure
- oxidative stress
- prognostic factors
- mesenchymal stem cells
- cell therapy