CD19 CAR T-cell(Guangdong Zhaotai Cell Bio-tech Co., LTD)

CD19 chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for relapsed/refractory diffuse large B-cell lymphoma (R/R-DLBCL), but challenges such as posttreatment failure and immune-related adverse events (AEs) persist. This study explores the gut microbiome as a predictive biomarker for CAR T-cell therapy outcomes and toxicity. Stool and serum samples from patients with R/R-DLBCL were analyzed at apheresis (47 samples) and 1 month after infusion (32 samples) using whole-genome sequencing metagenomics. When compared with healthy controls and newly-diagnosed DLBCL, R/R-DLBCL showed significant gut dysbiosis, characterized by increased Proteobacteria and Enterobacteriaceae. Responders had higher levels of Bacteroides fragilis, whereas nonresponders exhibited higher levels of Faecalibacterium prausnitzii. Functional metagenomic analysis suggested enrichment of inosine biosynthesis pathways in responders, and elevated serum inosine demonstrated an exploratory association with improved progression-free survival. Distinct microbial taxa and serum fatty acid profiles were also linked to CAR T-cell–related AEs, with higher acetate and butyrate levels in patients without AEs and increased isovalerate in those with AEs. These findings indicate that gut microbiome features—particularly Bacteroides fragilis and inosine metabolism—may serve as candidate biomarkers for CAR T-cell therapy outcomes and toxicity. However, given the exploratory nature of these analyses and the limited cohort size, results should be interpreted cautiously. Larger, prospective studies will be required to validate these observations and to assess the potential of microbiome-based strategies to optimize CAR T-cell therapy in R/R-DLBCL.

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent complication of CD19 CAR T-cell therapy. Although several biomarkers, particularly S100β, have been reported to be associated with ICANS, their biological significance and specificity remain unclear. We retrospectively studied adult patients treated with commercial CD19 CAR T cells between 2020 and 2024, focusing on early serum dynamics of S100β and neuron-specific enolase (NSE). Among 122 treated patients, 72 had complete paired biomarker measurements and were included; 21 (29%) developed ICANS at a median of 6 days after infusion. Prior CNS involvement was significantly more frequent in patients with ICANS (81% vs 35%). ΔS100β was higher in patients with ICANS compared with those without (0.03 vs 0.01 µg/L, p = 0.037), whereas ΔNSE showed no association with ICANS. In multivariable analysis, prior CNS involvement was the only independent factor associated with ICANS (OR 11.2), while ΔS100β did not retain significance. Neither biomarker correlated with ICANS severity or duration. These results indicate that early serum S100β variations mainly reflect baseline CNS vulnerability rather than ICANS-specific neurotoxicity, and that NSE provides no evidence of early neuronal injury detectable in serum.