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
{"title":"Metabolic tumor volume response after bridging therapy determines chimeric antigen receptor T-cell outcomes in large B cell lymphoma","authors":"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","doi":"10.1158/1078-0432.ccr-24-0830","DOIUrl":null,"url":null,"abstract":"Purpose: 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 and Methods: 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). Results: 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). Conclusions: 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.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":10.0000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1078-0432.ccr-24-0830","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: 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 and Methods: 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). Results: 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). Conclusions: 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.
期刊介绍:
Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.