Veracyte, Inc. announced that new data published on August 29, 2022 in Nature Medicineprovide the first evidence that the pre-treatment tumor microenvironment (TME) can impact response to chimeric-antigen-receptor (CAR) T-cell therapy among patients with large B-cell lymphoma (LBCL). The study findings demonstrated for the first time the prognostic and predictive capabilities of Veracyte's proprietary biomarkers among LBCL patients treated with CAR T-cell therapy. This study aimed to identify biomarkers associated with CAR T-cell therapy outcomes in patients treated with Kite's axicabtagene ciloleucel (axi-cel), a first-in-class anti-CD19 CAR T-cell therapy.

Study investigators conducted a retrospective analysis using Veracyte's Immunoscore Clinical Research (CR) and Immunosign 21 (IS21) assays, along with three custom panels (Immunoscore T-cell Exhaustion, TCE+ panels and Immunoscore Suppressive Cells panel) to compare pre-treatment TME patterns that were associated with improved response in Kite's ZUMA-1 study, the pivotal Phase 2 trial in adult patients with relapsed or refractory LBCL. Results published suggest that the pre-treatment tumor immune contexture was associated with, and potentially a major determinant of, clinical outcomes in ZUMA-1 patients. Improved clinical outcomes were more associated with high resolution pre-treatment immune contexture characterized by Immunoscore CR and Immunosign 21 rather than with general T-cell gene profiles and densities.

In the study, researchers noted rapid and broad changes across post-treatment TME immune programs associated with improved response, with marked decrease in B-cell lineage gene expression in responders' TME. Researchers also suggest that immune-based therapies with curative potential such as axi-cel should be considered in earlier lines of therapy where a larger percentage of patients have more favorable TME features and lower tumor burden, to potentially maximize clinical benefit.