Analysis of Colonic FDG Uptake and Association with Response and Toxicity to CART in LBCL Patients

Introduction Colonic uptake of fluorodeoxyglucose (FDG) has been shown to predict response to immunotherapy in patients with solid tumors, likely reflecting the colonic bacterial load and associated glycolytic flux and inflammatory status. As we previously demonstrated that a non-antibiotic-disrupted gut microbiome can impact the activity of chimeric antigen receptor T-cell therapy (CART). Objectives We sought to analyze the association of colonic FDG uptake with response and toxicity to CART in patients with large B-cell lymphoma (LBCL). Methods This is a single center retrospective study of LBCL patients treated with commercial axicabtagene ciloleucel between 01/2018 and 05/2022. Colonic FDG uptake was retrospectively measured on positron emission tomography scans obtained before initiation of lymphodepleting chemotherapy. Regions of interest were drawn manually on each transaxial slice around the outer boundaries of the five colonic regions (cecum, ascending, transverse, descending, and rectosigmoid) using MIM software 7.1.4. Uptake was measured using the standardized uptake value (SUV). Response was assessed according to 2014 Lugano criteria, and toxicity graded according to ASTCT scoring system. Results One-hundred and forty-nine patients were included in the analysis (Fig. 1). The median age was 59 years (range, 24-85), 98 (66%) were males and median serum LDH was 291 U/L (126-5323). Median SUVmax and SUVmean were 2.6 and 1.23 in the cecum, 2.34 and 1.29 in the ascending colon, 1.79 and 0.82 in the transverse colon, 1.61 and 0.87 in the descending colon, 2.07 and 1.01 in the sigmoid colon, respectively. Lower transverse colon SUVmax associated with elevated serum LDH (1.6 vs 2.03, p = 0.0029) and use of high-risk antibiotics (meropenem, cefepime, ceftazidime, and piperacillin tazobactam; 1.47 vs 1.82, p = 0.0464), and lower transverse colon SUVmean associated with elevated serum LDH (0.77 vs 0.95, p = 0.002). An increased SUVmean of the descending colon was significantly associated with decreased immune effector cell associated neurotoxicity syndrome rates, including any grade (0.97 vs 0.82, p = 0.0361), G2-4 (1.4 vs 1, p = 0.0031) and G3-4 (0.94 vs 0.79, p = 0.0158). An increased SUVmean of the cecum (1.47 vs 1.05, p = 0.0457) and ascending colon (1.31 vs 1.2, p = 0.0376) and an increased SUVmax of the ascending colon (2.38 vs 2.3, p = 0.0498) were significantly associated with day 90 complete response (CR). No statistically significant associations were observed between colonic FDG uptake and cytokine release syndrome or with CR at day 30. Conclusions Preliminary data demonstrates that colonic FDG uptake associates with selected response and toxicity to CART in LBCL. Larger prospective studies are needed to confirm these observations, to clarify its biological mechanisms, and to determine how tumor burden, antibiotic use, and microbiome may impact these findings.