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

J Rossi, P Paczkowski, YW Shen… - Blood, The Journal …, 2018 - ashpublications.org
J Rossi, P Paczkowski, YW Shen, K Morse, B Flynn, A Kaiser, C Ng, K Gallatin, T Cain…
Blood, The Journal of the American Society of Hematology, 2018ashpublications.org
After treatment with chimeric antigen receptor (CAR) T cells, interleukin-15 (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 …
Abstract
After treatment with chimeric antigen receptor (CAR) T cells, interleukin-15 (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, IL-17A, IL-8, and macrophage inflammatory protein 1α. 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 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. This trial was registered at www.clinicaltrials.gov as #NCT00924326.
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