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AACR 2022: Predicting Response/Resistance to Brexucabtagene Autoleucel in Mantle Cell Lymphoma

By: Vanessa A. Carter, BS
Posted: Wednesday, April 13, 2022

Vivian Changying Jiang, PhD, of MD Anderson Cancer Center, Houston, and colleagues performed multiomics profiling of patients with mantle cell lymphoma who relapsed after treatment with brexucabtagene autoleucel—an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. Presented during the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 771/27), these results reported that the mechanisms leading to CAR T-cell therapy resistance include enrichment of suppressive myeloid-derived-suppressor cells, elevated serum interleukin-2 (IL-2) receptor and checkpoint molecules, and T-cell exhaustion.

The investigators performed single-cell transcriptomic profiling for primary patient samples (n = 39) from 15 patients who were refractory to treatment (n = 1), relapsed (n = 5), or experienced a complete response (n = 14). Additionally, cytokine multiplex analysis was performed for plasma samples (n = 80) from 18 patients who were refractory to treatment (n = 1), relapsed (n = 5), or achieved a complete response (n = 17).

For patients in relapse, the fraction of CD4/CD8 cytotoxic T cells among total immune cells appeared to be significantly reduced when compared with those in remission or at before treatment. T-cell exhaustion at relapse was mediated by the upregulation of immune checkpoint molecules LAG3, TIGIT, and CD96, and ex vivo stimulation induced T-cell activation to produce IFNγ and IL-2 at remission, but not at relapse. Myeloid-derived suppressor cells were enriched at relapse.

Soluble checkpoint molecules TIM3, LAG3, PD-L1, and PD-L2 appeared to decrease significantly during remission when compared with baseline and baseline at relapse. Furthermore, soluble IL-2 receptor was also found to be significantly decreased at remission, although levels were elevated at relapse. Ex vivo stimulation with IL-2 plus soluble IL-2 receptor seemed to enhance cell growth compared with these molecules alone before treatment, but it lessened cell growth at relapse. Thus, this suggests that the soluble IL-2 receptor may have the potential to suppress T-cell activation and expansion.

Disclosure: For full disclosures of the study authors, visit

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