Right ventricular dysfunction in hematologic patients exposed to Chimeric Antigen Receptor (CAR)-T cells therapy: results from the prospective CARdio-TOX study

Abstract Background Chimeric antigen receptor-T (CAR-T) cells therapy is a pioneering treatment for haematologic malignancies (1). However, this novel paradigm of therapy is associated with cardiovascular (CV) toxicities, mainly related to cytokine release syndrome (CRS), an aberrant inflammatory activation. In the pivotal CARdio-TOX study, in the first week after treatment, a significant proportion of patients developed cancer therapy-related cardiac dysfunction (CTRCD), defined according the 2022 European Society of Cardiology Cardio-Oncology guidelines (1). In this study, we explored the detrimental effects of CAR-T cell administration on right ventricular (RV) function. Methods and Results. Sixty adult patients affected by haematologic malignancies were consecutively and prospectively evaluated at baseline, 7 and 30 days after CAR-T cells infusion through echocardiography, serum inflammatory and cardiac biomarkers (high sensitivity troponin I and natriuretic peptides). Incidence of RV CTRCD, defined as relative modifications of RV free wall longitudinal strain (RVFWLS)15% (2), was high at 7 days (50%). As well, RV global longitudinal strain (GLS) and RV fractional area change demonstrated significant deterioration at 7 days (p0.001 for both), while TAPSE not. In patients with RV CTRCD, we also found higher levels of high-sensitivity troponin I (p =0.01), natriuretic peptides (p =0.004) and lower LV global longitudinal strain values (p =0.015). Conclusions To our knowledge, this is the largest prospective study focused on CAR-T cell cardiotoxicity. We firstly explored modifications of RV function through comprehensive echocardiography, revealing high incidence of CTRCD at 7 days. Further research on potential mechanisms and integration with other imaging modalities are necessary.