Reasons for Discordance Among Imaging‐based Response Criteria In Lymphoma Patients Receiving CAR T‐cell Therapy

Abstract

Introduction: Chimeric antigen receptor T cell therapy (CART) has emerged as an effective cell-based immunotherapy using patient-derived T cells. Modified CAR T cells are used for the treatment of relapsed or refractory (r/r) lymphoma with expression of a CD19 antigen specific receptor. CART prolongs survival for patients with r/r lymphoma compared to historical controls. In the currently ongoing phase III trials, treatment response is assessed using the Lugano criteria from 2014. In the recent years, new imaging criteria for lymphoma have been published. Discrepancies among these different response criteria for lymphoma under CART were recently shown. We evaluated reasons for discordance among different response criteria and their relation to overall survival (OS). Methods: Consecutive large B-cell lymphoma (LBCL) and mantle-cell lymphoma (MCL) patients with baseline and follow-up imaging 30, and 90 days after CART infusion were included. For each patient, up to 6 Tagret lesions, non-target lesions, and the spleen were 3D-segmented. Overall response was determined based on Lugano criteria, Cheson criteria, response evaluation criteria in lymphoma (RECIL) and lymphoma response to immunomodulatory therapy criteria (LYRIC). Overall response rate (ORR) and rates of progressive disease (PD) were determined. For each criterion reasons for PD were analyzed in detail. Results: 41 patients were included (median age: 64 years, 41% female). ORR was 68%, 68%, 63%, and 68% at FU2 by Lugano, Cheson, RECIL, and LYRIC, respectively. PD rates differed among criteria with 32% by Lugano, 27% by Cheson, 17% by RECIL, and 17% by LYRIC. Dominant reasons for PD according to Lugano were target lesion (TL) progression (84.6%), new appearing lesions (NL; 53.8%), non-TL progression (27.3%), and progressive metabolic disease (PMD; 15.4%). Deviations among the criteria were largely explained by PMD of preexisting lesions that are defined as PD only by Lugano and non-TL progression, which is not defined as PD by RECIL and in some cases classified as indeterminate response by LYRIC. Interestingly, grouping patients according to focality of progressive target lesions showed a significant trend for OS stratification (p = 0.036). The research was funded by: Förderung für Forschung und Lehre (FöFoLe) project number 1147” of the Medical Faculty of Ludwig Maximilian University (LMU) Munich and the Bavarian Cancer Research Center (BZKF) to M.W.. The work was further supported by the Else-Kröner-Fresenius Stiftung (to V.B.) and the German Cancer Consortium DKTK (to V.B.). Keywords: Cellular therapies, Diagnostic and Prognostic Biomarkers, PET-CT Conflicts of interests pertinent to the abstract. V. Blumenberg Consultant or advisory role: Kite/Gilead Honoraria: Kite/Gilead, Janssen, Novartis Research funding: BMS/Celgene, Kite/Gilead, Novartis, Roche, Takeda K. Rejeski Honoraria: Novartis Research funding: Kite/Gilead Educational grants: Kite/Gilead V. Buecklein Honoraria: Amgen, Kite/Gilead, Novartis, Pfizer Research funding: Celgene/BMS, Kite/Gilead C. Schmidt Educational grants: Kite/Gilead M. von Bergwelt-Baildon Consultant or advisory role: Astellas, BMS, Kite/Gilead, Miltenyi, Mologen, MSD Sharp & Dohme, Novartis, Roche Honoraria: Astellas, BMS, Kite/Gilead, Miltenyi, Mologen, MSD Sharp & Dohme, Novartis, Roche Research funding: Astellas, BMS, Kite/Gilead, Miltenyi, Mologen, MSD Sharp & Dohme, Novartis, Roche M. Subklewe Consultant or advisory role: Amgen, Astra Zeneca, Aven Cell, BMS/Celgene, CDR-Life, Gilead, Incyte Biosciences, Janssen, Miltenyi Biotec, Molecular Partners, Novartis, Pfizer, Roche, Takeda Research funding: Amgen, BMS/Celgene, Gilead, Janssen, Miltenyi Biotec, Morphosys, Novartis, Roche, Takeda W. Kunz Consultant or advisory role: Bristol Myers Squibb