Organ-specific depth of response to CD19-directed CAR T-cell therapy in B-cell lymphomas

Background CD19-directed chimeric antigen receptor T cell therapy (CART) has transformed treatment of relapsed or refractory (r/r) large B cell lymphoma (LBCL); however, organ-specific response patterns and depth of response (DoR) remain insufficiently characterized. This study evaluated organ-specific imaging response and the impact of spatial disease patterns on progression-free survival (PFS) and overall survival (OS). Materials and methods In this retrospective single-center study, 109 consecutive patients with r/r LBCL treated with CD19-directed CART between January 2019 and May 2025 were included. Baseline and follow-up CT or PET/CT was analyzed using structured lesion tracking. Up to six target lesions per patient were assessed according to Lugano criteria, and the sum of the products of diameters (SPD) was calculated. DoR was defined as percentage change in SPD from baseline. Associations with PFS and OS were evaluated using Kaplan–Meier analysis and Cox regression. Results Among 109 patients (median age, 65 years [IQR, 57–71]), 65 (59.6%) had extranodal disease at baseline. Baseline tumor burden was higher in patients with extranodal than nodal disease (median SPD, 3573 mm 2 [IQR, 1314–9708] versus 1998 mm 2 [IQR, 1347–2921]). DoR was comparable between nodal and extranodal lesions at both time points (− 62.1% vs. − 65.6% and − 77.9% vs. − 78.1%); this comparability at the second follow-up may partly reflect differential attrition, as extranodal patients were more likely to be lost to follow-up before this timepoint. Despite similar tumor reduction, median PFS was 306.5 days in nodal versus 90 days in extranodal disease. Baseline tumor burden (SPD) was independently associated with both PFS and OS (HR per doubling of SPD 1.17 and 1.21, respectively). Pleural, hepatobiliary, and adrenal involvement showed the strongest associations with adverse outcomes in this exploratory, hypothesis-generating organ-level analysis; pleural involvement remained independently associated with PFS and OS, though organ-specific subgroups were small ( n = 7–19) and estimates should be interpreted with caution. Conclusion Tumor reduction occurs in nodal and extranodal disease after CART, but outcomes depend on anatomical disease distribution. Pleural and hepatobiliary involvement emerged as candidate high-risk imaging phenotypes in this exploratory analysis, warranting confirmation in larger, multicenter cohorts. Organ-specific assessment may provide information beyond global tumor burden.