Metabolic Tumor Volume Response after Bridging Therapy Determines Chimeric Antigen Receptor T-Cell Outcomes in Large B-Cell Lymphoma

Purpose: Greater disease burden is a well-established predictor of poorer outcomes following chimeric antigen receptor T-cell (CAR T) therapy. Although bridging therapy (BT) is widely used between leukapheresis and CAR T infusion, limited data have evaluated the impact of BT on CAR T outcomes. In this study, we hypothesized that the quantitative dynamics of radiomic cytoreduction during bridging are prognostic. Experimental Design: Patients with large B-cell lymphoma treated with CD19-CAR T from 2016 to 2022 were included in the study. Metabolic tumor volume (MTV) was determined for all patients on pre-leukapheresis PET and on post-BT/pre-infusion PET in those who received BT. Patients were stratified into "High"and "Low"disease burden using an MTV cutpoint of 65.4cc established by maximally selected log-rank statistic for progression-free survival (PFS). Results: Of 191 patients treated with CAR T, 144 (75%) received BT. In the BT cohort, 56% had a reduction in MTV post- BT. On multivariate analysis, the MTV trajectory across the bridging period remained significantly associated with PFS (P < 0.001); however, notably, patients with improved MTV (High- >Low) had equivalent PFS compared with those with initially and persistently low MTV (Low->Low; HR for High->Low MTV: 2.74; 95% confidence interval, 0.82-9.18). There was a reduction in any grade immune effector cell-associated neurotoxicity syndrome in the High->Low MTV cohort as compared with the High->High MTV cohort (13% vs. 41%; P = 0.05). Conclusions: This is the first study to use radiomics to quantify disease burden pre- and post-BT in a large real-world large B-cell lymphoma cohort. We demonstrate that effective BT can enable initially high-disease burden patients to achieve post- CAR T outcomes comparable with low-disease burden patients.