Metabolic tumor volume response after bridging therapy determines chimeric antigen receptor T-cell outcomes in large B cell lymphoma.

in Clinical cancer research : an official journal of the American Association for Cancer Research by Harper Hubbeling, Doris Leithner, Emily A Silverman, Jessica Flynn, Sean Devlin, Gunjan Shah, Beatrice Fregonese, Beatriz Wills, Akshay Bedmutha, Ana Alarcon Tomas, Allison Parascondola, Amethyst Saldia, Ivan Landego, Carla Hajj, Alexander P Boardman, Parastoo B Dahi, Arnab Ghosh, Sergio Giralt, Richard J Lin, Jae Park, Michael Scordo, Gilles Salles, Joachim Yahalom, M Lia Palomba, Heiko Schöder, Miguel-Angel Perales, Roni Shouval, Brandon S Imber

TLDR

  • The study looked at how well bridging therapy (BT) works before chimeric antigen receptor T-cell therapy (CART) for patients with large B-cell lymphoma (LBCL). The study found that patients who had a lot of disease before BT had the same outcomes after CART as patients who had less disease before BT. The study also found that the amount of disease reduction during BT was important in predicting how well patients did after CART. The study highlights the importance of using radiomics to measure disease burden before and after BT, which could help doctors make better treatment decisions for patients.

Abstract

Greater disease burden is a well-established predictor of poorer outcomes following chimeric antigen receptor T-cell therapy (CART). While bridging therapy (BT) is widely used between leukapheresis and CAR T infusion, limited data has evaluated the impact of BT on CART outcomes. In this study, we hypothesized that the quantitative dynamics of radiomic cytoreduction during bridging are prognostic. Patients with large B-cell lymphoma (LBCL) treated with CD19-CART from 2016-2022 were included. 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). Of 191 patients treated with CART, 144 (75%) received BT. In the BT cohort, 56% had any reduction in MTV post-BT. On multivariate analysis, 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 to those with initially and persistently low MTV (Low->Low) (HR for High->Low MTV: 2.74, CI: 0.82-9.18). There was a reduction in any Grade ICANS in the High->Low MTV cohort as compared to High->High (13 vs. 41%, p=0.05). This is the first study to use radiomics to quantify disease burden pre- and post-BT in a large real world LBCL cohort. We demonstrate that effective BT can enable initially high-disease burden patients to achieve post-CART outcomes comparable to low-disease burden patients.

Overview

  • The study focuses on the impact of bridging therapy (BT) on outcomes following chimeric antigen receptor T-cell therapy (CART) for patients with large B-cell lymphoma (LBCL). The hypothesis is that the quantitative dynamics of radiomic cytoreduction during bridging are prognostic. The study includes patients treated with CD19-CART from 2016-2022 and determines metabolic tumor volume (MTV) for all patients on pre-leukapheresis PET and on post-BT/pre-infusion PET in those who received BT. Patients are 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).

Comparative Analysis & Findings

  • The study compares outcomes observed under different experimental conditions or interventions, specifically the impact of BT on CART outcomes. The results show that effective BT can enable initially high-disease burden patients to achieve post-CART outcomes comparable to low-disease burden patients. The study also demonstrates that MTV trajectory across the bridging period remained significantly associated with PFS, and notably patients with improved MTV (High->Low) had equivalent PFS compared to those with initially and persistently low MTV (Low->Low).

Implications and Future Directions

  • The study's findings suggest that effective BT can improve outcomes following CART for patients with LBCL. The study also highlights the importance of radiomics in quantifying disease burden pre- and post-BT, which could be used to inform treatment decisions and personalize CART therapy. Future research could explore the use of radiomics in predicting response to CART and identifying subgroups of patients who may benefit from BT. Additionally, the study's findings could inform the development of new bridging strategies that optimize disease burden reduction and improve CART outcomes.
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