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Impact of Ibrutinib on T-Cell Responses in CLL

By: Vanessa A. Carter, BS
Posted: Friday, May 28, 2021

According to Clare Sun, MD, of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, and colleagues, ibrutinib seems to influence T-cell activation and polarization, but whether T cells are associated with clinical response is as yet still unknown. These researchers profiled the T-cell compartment in patients with chronic lymphocytic leukemia (CLL) to identify any possible response. Published in Clinical Cancer Research, their results may provide the “missing link between antigen specificity and function of T cells in patients with CLL treated with ibrutinib.”

The phase II trial focused on 26 patients with treatment-naive, relapsed, or refractory CLL on ibrutinib monotherapy. Peripheral blood mononuclear cell samples from these patients were obtained before treatment, during response, and at either sustained remission or disease progression. High-throughput T-cell receptor-ß sequencing was performed in 77 samples from these patients; the utilization of this sequencing in CD4-positive and CD8-positive T cells, along with granzyme B expression, was evaluated by flow cytometry.

Of the total, 19 patients had a chromosome 17p deletion, 17 did not have immunoglobulin heavy chain variable (IGHV) mutations, and 11 had relapsed or refractory disease. Partial and complete responses were achieved in 24 and 2 patients, respectively. At the median follow-up of 68 months, 12 participants developed progressive disease, whereas others remained in remission.

At the time of response, the study authors observed increased clonality of the T-cell receptor’s habits. T-cell receptor clonality decreased in patients with disease progression, yet it remained consistent in those with sustained remission. A predominance of CD8-positive cells among expanded clonotypes was revealed by flow cytometry. Of note, the T cells of patients who responded were cytotoxic against autologous CLL cells, with the depletion of expanded clonotypes reducing CLL cell death.

Disclosure: For full disclosures of the study authors, visit clincancerres.aacrjournals.org.



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