Abstract 3199: Radiomic features associated with anti-tumor activity in Non-Hodgkin lymphoma patients treated with CD19 directed allogenic CAR T therapy

Abstract Introduction: Radiomic features extracted from 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG PET/CT) provide valuable insight into the anti-tumor activity of CD19-directed CAR T therapy in patients with non-Hodgkin lymphoma (NHL). This study examined an integrative approach combining radiomic features and patient-specific attributes to determine if these parameters are associated with anti-tumor response across two investigational allogeneic CD19-directed CAR T programs, CTX110 and CTX112. CTX112 contains two novel CRISPR-mediated gene edits to Regnase-1 and Transforming Growth Factor Beta Receptor 2 (TGFBR2), which are intended to increase CAR T cell expansion, functional persistence and potency. Methods: Patients with R/R NHL of a variety of histologies were given LD chemo followed by either CTX110 or CTX112. Radiomic features were extracted from [18F] FDG PET/CT scans at baseline (screening) and the first assessment at day 28. 48 patients treated with CTX110 and CTX112 at four dose levels (3x107 [DL1], 1x108 [DL2], 3x108 [DL3], and 6x108 [DL4] CAR+ T cells) were analyzed. Potential features associated with anti-tumor activity were identified at three different levels: (1) subject-level, (2) total tumor burden-level, and (3) lesion-level. To understand the interplay between CAR T cells and tumor lesions, multiple feature selection techniques were employed to delineate different sets of features that correlate with anti-tumor activity. Results: Median values for the total tumor burden (TB) as measured by the total metabolic tumor volume (MTV) for patients treated with CTX110 were less than CTX112 (CTX110 = 96 [38 to 291] mL and CTX112 = 146 [91 to 187], median [IQR]) indicating that the patients treated with CTX112 may have been more difficult to treat. CTX110 and CTX112 both showed dose-dependent activity, producing larger reductions in MTV with higher CAR T cell doses. However, CTX112 was observed to have similar % MTV reduction at 3x107 cells (DL1) as CTX110 does at 3x108 cells (DL3), suggesting CTX112 possess an estimated 10-fold higher anti-tumor activity than its predecessor. By estimating the effector to target (E:T) ratio in patients, whereby the CAR+ cells dose is normalized to the baseline MTV, patients with high E:T ratios were shown to have increased anti-tumor activity compared to low ratios for both CTX110 and CTX112. Conclusions: Multivariate analysis of [18F] FDG PET/CT scans shows that CTX110 and CTX112 exhibit consistent dose-dependent anti-tumor activity, as measured by decrease in MTV, across patients with diverse radiomic features. Across multiple methods estimating MTV-reduction efficacy, CTX112 is approximately 10-fold more efficacious than CTX110, despite the CTX112-treated cohort containing patients with baseline radiomic features associated with poor response. Citation Format: Andrew R. Dunn, Shashwat Deepali Nagar, Donald J. Kirsch, Leah M. Williams, Annie Y. Weaver, Philipp M. Altrock, William S. Denney, Chan Y. Cheah, P. Joy Ho, Joseph P. McGuirk, Paul Shaughnessy, Constantine S. Tam, Armin Ghobadi. Radiomic features associated with anti-tumor activity in Non-Hodgkin lymphoma patients treated with CD19 directed allogenic CAR T therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3199.