Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells associate with clinical outcomes in NHL

Abstract

After treatment with chimeric antigen receptor (CAR) T cells, interleukin (IL)-15 elevation and CAR T-cell expansion are associated with non-Hodgkin lymphoma (NHL) outcomes. However, the association of preinfusion CAR product T-cell functionality with clinical outcomes has not been reported. A single-cell analysis of the preinfusion CD19 CAR product from patients with NHL demonstrated that CAR products contain polyfunctional T-cell subsets capable of deploying multiple immune programs represented by cytokines and chemokines including interferon-γ (IFN-γ), IL-17A, IL-8, and macrophage inflammatory protein 1-α. A prespecified T-cell polyfunctionality strength index (PSI) applied to preinfusion CAR product was significantly associated with clinical response, and PSI combined with CAR T cell-expansion or pretreatment serum IL-15 levels conferred additional significance. Within the total product cell population, associations with clinical outcomes were greater with polyfunctional CD4+ T cells compared with CD8+ cells. Grade 3+ cytokine release syndrome was associated with polyfunctional T cells, and both grade 3+ neurologic toxicity (NT) and antitumor efficacy were associated with polyfunctional IL-17A–producing T cells. The findings in this exploratory study show that a preinfusion CAR product T-cell subset with a definable polyfunctional profile has a major association with clinical outcomes of CAR T-cell therapy.