Baseline Immunologic State Affects CAR-T Cell Response in LBCL

By Blood Cancers Today Staff Writers - Last Updated: February 2, 2024

The baseline immunologic state of a patient with large B-cell lymphoma (LBCL) could affect response to CAR T-cell therapy, according to an abstract presented at the 65th ASH Annual Meeting and Exposition. This process could be affected through the modulation of the T-cell apheresis product composition and promotion of a more favorable circulating immune compartment prior to therapy.

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Katie Maurer, MD, PhD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and colleagues collected serial peripheral blood mononuclear cell samples from patients with relapsed or refractory LBCL treated with axicabtagene ciloleucel (axi-cel). Samples were taken from day –30 to +28 relative to receipt of the CAR T-cell infusion. In addition, the researchers collected bag washings from infusion products (IPs).

There was no difference in post-infusion circulating immune subsets among patients who did or did not respond to CAR T-cell therapy. However, the researchers did find that the proportion of B cells was increased in patients who had responded (P=0.012). Additionally, circulating B cells were highest among complete responders. When the responders were separated into complete responders and those who did not have complete response, complete responders had significantly increased frequency of circulating B cells (P=.0057).

Responders also had a higher lymphocyte to monocyte ratio compared with nonresponders (P=.22). This was confirmed in a larger flow cytometry cohort of patients and validated in a cohort of patients treated with commercial axi-cel at Dana-Farber Cancer Institute from 2019 to 2022.

Using scRNA-seq analysis, the researchers found that IP cells demonstrated an increased proportion of CD8 T cells in responders compared with nonresponders (P=.024) and showed a trend toward increased T effector memory expression profile (P=.079). The researchers also observed greater clonal expansion of CD8 T effector memory cells in responders compared with nonresponders.

“These data implicate clonal expansion and T-cell activation at infusion as key indicators of CAR-T response,” the researchers wrote. “These features, detectable by highly accessible clinical measures, could be leveraged for improved patient selection and enhanced CAR-T manufacturing.”

Reference

Maurer K, Grabski IN, Houot R, et al. Baseline immune state and T cell clonal kinetics are associated with response to CAR-T therapy in large B-cell lymphoma. Abstract #223. Presented at the 65th ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.

Post Tags:ASHNEWS2023
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