Dynamics of Radiomic Features Following Bridging Therapy Determine Cd19 Chimeric Antigen Receptor (Car) T‐cell Therapy Outcome

Introduction: Higher disease burden is associated with poor chimeric antigen receptor T-cell (CAR T) outcomes. Bridging therapy (BT) is widely used to debulk or palliate between apheresis and CAR T infusion. We studied whether the dynamics of radiomic cytoreduction during bridging are prognostic. Methods: Large B-cell lymphoma (LBCL) patients (pts) treated with anti-CD19 CAR T cells were stratified into 4 BT groups: (1) no BT (2) systemic therapy (ST) (including steroids) (3) radiotherapy (RT) and (4) combined ST/RT. To better assess the impact of BT, we created an MTV analysis cohort of pts who received BT and had repeat PET post-BT but pre-CAR T infusion. Max SUV and total metabolic tumor volume (MTV) using an automated method and SUV4 threshold were calculated for all pts off the pre-apheresis PET and for the analysis cohort on the post-BT PET. Pts in the analysis cohort were ordered into equal sized tertiles by absolute MTV amount first pre-apheresis and then again post-BT. To quantify impact of BT cytoreduction, we created 5 risk groups from the analysis cohort per degree of MTV change during BT: (a) High MTV (highest MTV tertile both pre and post BT) (b) Mid MTV (middle tertile pre and post BT) (c) Low MTV (lowest tertile pre and post BT) (d) Improved MTV (tertile decreased post BT) and (e) Progressing MTV (tertile increased post BT). Overall survival (OS) post-CAR T was estimated by Kaplan Meier. Results: 198 pts with LBCL (80%), high grade BCL (17%) or primary mediastinal BCL (3%) received CAR T (49% axicabtagene, 32% tisagenlecleucel, 19% lisocabtagene). Max SUV at apheresis was 18.5 (interquartile range, IQR 9.8 – 25.3) and MTV was 45.7 (IQR 5.7–167). 51 (26%) received no BT, 116 (59%) had ST, 20 (10%) had RT, 11 (6%) had ST/RT. Median OS was 13.9 mo overall, and 20.6 mo, 12.1 mo, 26.4 mo and 5.5 mo for the no BT, ST, RT and ST/RT groups, respectively. The MTV analysis cohort included 112/147 BT (76%) pts (n = 88 ST, n = 16 RT, n = 8 CMT). Median baseline max SUV was 20.0 (IQR 13.7—26.1), which was reduced 28% to 14.4 (IQR 5.5—22.1) post-BT. Median baseline MTV was 67.2cc (IQR 15.0—218.7) which was reduced 42% to 39.0cc (IQR 2.1—235.2) post-BT. Roughly half (53%) had any degree of quantitative cytoreduction post-BT (Figure A). The MTV burden both pre-apheresis and post-BT was significantly associated with post-CAR T OS (Figure B, C, p = 0.004, p < 0.0001, respectively). Median OS for the High MTV (n = 22), Mid MTV (n = 17) and Low MTV (n = 22), Improved MTV (n = 24) and Progressing MTV (n = 27) risk groups was 4.1, 15.5, 21.6, 13.6 and 10.1 mo, respectively (Figure D). The research was funded by: The Leukemia and Lymphoma Society Translational Research Program (TRP), the Memorial Sloan Kettering Cancer Center Comedy versus Cancer Grant Program, the Connecticut Cancer Foundation, the Steven A. Greenberg Award in Lymphoma, as well as the Memorial Sloan Kettering Cancer Center Support Grant P30 CA008748. Keywords: cellular therapies, PET-CT, radiation therapy Conflicts of interests pertinent to the abstract G. L. Shah Consultant or advisory role: DSMB for ArcellX Research funding: Research funding to the institution from Janssen, Amgen, Beyond Spring, and BMS P. B. Dahi Consultant or advisory role: Curio Science LLC, Kite Pharmaceuticals, OncLive, Targeted Oncology S. Giralt Consultant or advisory role: Amgen, Actinuum, Celgene, Johnson & Johnson, Janssen, JAZZ Pharmaceuticals, Takeda, Novartis, Kite, Spectrum Pharma Research funding: Amgen, Actinuum, Celgene, Johnson & Johnson, Miltenyi, Takeda, Omeros M. Scordo Consultant or advisory role: McKinsey & Company, Angiocrine Bioscience, Inc., and Omeros Corporation, Kite – A Gilead Company Honoraria: i3Health and Medscape for CME-related activity Research funding: Angiocrine Bioscience, Inc., and Omeros Corporation G. Salles Consultant or advisory role: Abbvie, Atbtherapeutics, Bayer, Beigene, BMS/Celgene, Debiopharm, Epizyme, Genentech/Roche, Genmab, Incyte, Ipsen, Janssen, Kite/Gilead, Loxo/Lilly, Molecular Partners, Morphosys, Nordic Nanovector, Novartis, Regeneron, Takeda Stock ownership: Owkin M. L. Palomba Consultant or advisory role: Synthekine, Cellectar, Beigene, Kite, BMS M. Perales Consultant or advisory role: on DSMBs for Cidara Therapeutics, Medigene, and Sellas Life Sciences, and the scientific advisory board of NexImmune Stock ownership: NexImmune, Omeros and OrcaBio Honoraria: Adicet, Allovir, Caribou Biosciences, Celgene, Bristol-Myers Squibb, Equilium, Exevir, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Syncopation, VectivBio AG, and Vor Biopharma Research funding: institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis