Radiomic Features Prognosticate Treatment Response in CAR-T Cell Therapy

<b>Background</b>: Diffuse large B-cell lymphomas (DLBCLs) are the most common, aggressive disease form that accounts for 30% of all lymphoma cases. Identifying patients who will respond to these advanced cell-based therapies is an unaddressed challenge. <b>Methods</b>: We propose to develop a radiomics- (quantitative image metric) based signature on the patients' imaging scans (positron emission tomography/computed tomography, PET/CT) and use these metrics to prognosticate response to axi-cel (axicabtagene ciloleucel), autologous CD19 chimeric antigen receptor (CAR) T-cell (CAR-T) therapy. We curated a cohort of 155 patients with relapsed/refractory (R/R) DLBCL who were treated with axi-cel. Using their baseline image scan (PET/CT), the largest lesions related to nodal/extra-nodal disease were identified and characterized using imaging metrics (radiomics). We used principal component (PC) analysis to reduce the dimensionality of these features across the functional categories (size, shape, and texture). We evaluated the prognostic ability of radiomic-based PC to treatment response (1-year), measured by overall survival (OS) and progression-free survival (PFS). <b>Results</b>: We found that radiomic PC was prognostic of overall survival (Shape-PC, q < 0.013/0.0108, Size-PC, q < 0.003/0.0088), in CT/PET, respectively. In comparison, the metabolic tumor volume (MTV) was prognostic (q < 0.0002/0.0007). The radiomic PCs across the functional categories showed moderate to weak correlation with MTV, Spearman's ρ of 0.44/0.35/0.27, and 0.45/0.36/0.55 for Size/Shape/Texture-PC1 obtained on PET and CT, respectively. <b>Conclusions</b>: We found radiomic PC based on size and shape metrics that are able to prognosticate treatment response to CAR-T therapy.