Vascular inflammation in patients undergoing CD19 chimeric antigen receptor (CAR)-T cells for hematologic malignancies: a call for cardiovascular surveillance

Abstract Background Chimeric antigen receptor (CAR)-T cell therapy has shown effectiveness in advanced hematological malignancies. As well, evidence is growing on potential cardiotoxic implications of CAR-T cell exposure. However, effects of this therapy on vascular inflammation are unknown. Methods Patients treated with CAR-T cells infusion for relapsed or refractory B- cell aggressive lymphoma with available baseline and 30-day post CAR-T 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) were retrospectively analysed. Maximum standardized uptake values (SUVmax) of arterial and venous walls were calculated. Routine blood analysis results were collected and overtime changes in inflammatory markers were expressed as a Delta (Δ) during the first 14 days after infusion. The population enrolled was stratified according to the complete response to cellular therapy. Results Among the 35 patients finally included, segment-by-segment comparisons between baseline and 30-day PET/CT did not differ significantly. Veins exhibited lower mean SUV values compared to arteries (β = -0.18, 95% CI -0.27, -0.08, p 0.001). The interaction effect between time and response was statistically significant (β = -0.15, 95% CI -0.27, -0.03, p = 0.015); in particular, responders showed an overall increase in SUV values over time, while non-responders exhibited a decrease. As well, imaging modifications observed through PET/CT between these groups were accompanied by consensual changes in inflammatory and endothelial damage biomarkers (e.g., C reactive protein and mEASIX score). Conclusions Our results highlight higher vascular inflammation in patients considered as disease-responders after CAR-T cell therapy. These preliminary observations require confirmation in large-scale, prospective studies and call for patient-tailored cardiovascular surveillance.