439 Cardiovascular safety of chimeric antigen receptor (CAR) T cell therapy

BackgroundOver the past six years, chimeric antigen receptor (CAR) T cell therapy has shown great efficacy and promise for the treatment of hematologic malignancies and research is ongoing in a variety of other disease areas.1 Cardiovascular events are serious potential side effects of many oncological therapies, but have only been evaluated retrospectively in the context of CAR T cells and thus mainly in symptomatic patients in the respective study cohorts.2 In a patient population that is already heavily pretreated and therefore at increased risk, our aim was to prospectively evaluate the incidence of cardiotoxicity. Additionally, we analyzed the importance of cardiac biomarkers and cardiac risk factors in relation to cardiac events and all-cause mortality (ACM).MethodsThis observational study included patients who received CAR T cells at the University Hospital of Heidelberg between October 2018 and October 2022. ACM was defined as the primary endpoint of the study, while cardiotoxicity, determined by clinical syndromes such as a decrease in the ejection fraction, served as the secondary endpoint. Monitoring included 2D echocardiography, 12-lead electrocardiogram, as well as cardiac biomarkers (highly sensitive troponin T (hs-cTnT); brain N-terminal natriuretic peptide (NT-proBNP)) at multiple timepoints, starting before lymphodepleting chemotherapy and continuing through 180 days after CAR T-cell infusion.ResultsA total of 137 patients with a median age of 60 years (range 20–83, 72% male) were included in the study. During the follow-up, 46 patients deceased (34%), while the secondary endpoint was met by 93 patients (68%). No major adverse cardiac events (MACE) were reported in the study cohort and no baseline parameter predicted an increased cardiac risk. However, a 35%-cutoff for hs-cTnT change from lymphodepletion to within the first 14 days after CAR T cell infusion was identified, which was predictive not only for patients with an increased ACM (35%: OR 2.26, 95%-CI 1.00–5.17; p=0.050) but also for patients at risk of cardiac events. A continuous increase in significance for predicting survival was observed with increasing hs-cTnT change (e.g., 60%: OR 6.18, 95%-CI 2.28–18.19; p