The ability of chimeric antigen receptor (CAR) T-cells to perform multiple functions is associated with improved outcomes for patients with advanced non-Hodgkin lymphoma, offering a biomarker for response, according to a retrospective analysis presented at the 2017 American Association for Cancer Research Annual Meeting (April 1-5; abstract 2990).
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Researchers from Kite Pharmaceuticals conducted a study – using data from 20 patients enrolled in a previous study examining axicabtagene ciloleucal (KTE-C19) for non-Hodgkin Lymphoma – to assess the correlation between objective responses and single-cell CAR T therapy. Results of the assessment showed that objective responses correlated with single-cell CAR T polyfunctional strength index (PSI; P = .0119). Approximately 20% to 25% of CAR T-cells were polyfunctional.
Additionally, researchers found that post-infusion T-cell proliferation was associated with objective response (P = .0326). By combining PSI and T-cell expansion, researchers observed an increased correlation between the markers and objective response (P = .0046).
Implications of these findings, researchers suggest, are that PSI and T-cell expansion may help predict which patients with non-Hodgkin lymphoma are likely to respond to CAR T-cell therapy.
"PSI is a key attribute of CAR T-cell products that can be utilized to optimize product potency testing and facilitate the design of more efficacious T-cell products," said John Rossi, Kite Pharma, who presented the data at the meeting (April 4, 2017). "T-cell PSI was associated with objective responses in non-Hodgkin lymphoma but the combined index of PSI and CAR T-cell expansion has a stronger association with response."
Common adverse events associated with CAR T-cell therapy are related to the release of cytokines, which leads researchers to believe that PSI may be a predictor of toxicity as well.
Data from the retrospective analysis are being finalized for publication in a medical journal.
“Through this research, we were able to highlight the important role a functionally versatile subpopulation of CAR T-cells may play in the fight against cancer, leading to new ways to characterize and optimize T-cell products," said Adrian Bot, MD, vice president, Kite, Translational Medicine, in a statement (April 4, 2017). – Zachary Bessette
