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SummaryRecent 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.
SummaryRecent 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.
BackgroundAlthough numerous studies confirmed the marked efficacy of chimeric antigen receptor T cells (CAR-T cells) in many hematologic malignancies, severe cardiovascular toxicities remain to be a major obstacle when incorporating this technology. Furthermore, previous individual investigations regarding the cardiovascular toxicities of CAR-T cell therapy also reported controversial conclusions. Therefore, a meta-analysis was performed to further evaluate the impacts of CAR-T cell therapy on cardiovascular toxicities.MethodsThe PubMed, Embase, Web of Science, and ClinicalTrials.gov databases were searched for eligible studies up to April 2022. All analyses were carried out using the R 4.1.0 software.ResultsEventually, 25 related studies consisting of 2,059 patients were enrolled in the current meta-analysis. We discovered that the pooled incidence rate of the all-cause mortality rate was 14.1% and that the pooled incidence rates of overall cardiovascular (CV) events and CV events with cytokine release syndrome (CRS) grade ≥ 2 were 25.6% and 14.2%, respectively. The pooled incidence of hypotension was 28.6%. Further analysis showed that the incidence rates of arrhythmias, cardiovascular dysfunction, heart failure (HF), CV deaths, acute coronary syndrome (ACS), cardiomyopathy, cardiac arrest, and other CV events were 19.2%, 8.0%, 5.3%, 1.8%, 2.5%, 2.9%, 1.3%, and 1.9%, respectively.ConclusionCancer patients treated with CAR-T cell therapy were at risk for cardiovascular toxicities, of which the most common cardiovascular events were arrhythmias, cardiovascular dysfunction, and heart failure. These findings would contribute to achieving more rational and individualized use of CAR-T cells in clinical treatment.
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