Lenalidomide Induces Immunity, Produces Clinical Response in CLL

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Immune changes in the tumor microenvironment were associated with clinical response to lenalidomide in patients with chronic lymphocytic leukemia.
Immune changes in the tumor microenvironment were associated with clinical response to lenalidomide in patients with chronic lymphocytic leukemia.

Findings from a study published in the Journal of Immunology linked immunomodulation of the tumor microenvironment to clinical response to lenalidomide in patients with chronic lymphocytic leukemia (CLL).1

“In this study, we report changes in the immune microenvironment in patients with CLL treated with single-agent lenalidomide and associate the immunologic effects of lenalidomide with antitumor response,” the study authors wrote.

Patient samples were obtained from a phase 2 trial in which patients with relapsed CLL or small lymphocytic lymphoma were treated with lenalidomide (ClinicalTrials.gov Identifier: NCT00465127). In the trial, patients received lenalidomide at 10 mg or 20 mg daily, cycled 3 weeks on, 3 weeks off, for up to 8 cycles.

Soon after initial treatment with lenalidomide, patients had increased levels of T cells in the tumor microenvironment; the T cells had Th1-type polarization. Gene expression profiling revealed that IFN-γ and many of its target genes became upregulated after treatment with lenalidomide. Only patients who had a clinical response showed IFN- γ–mediated Th1 response. Deep sequencing of TCR genes showed that T-cell repertoire diversity dropped after lenalidomide treatment and select clonotypes expanded in patients who had a clinical response.

To confirm the findings, the researchers performed in vitro assays on samples obtained from patients with treatment-naive CLL who were in an observational study (ClinicalTrials.gov Identifier: NCT00923507). Exposure of T cells and CLL cells to lenalidomide in vitro revealed lenalidomide-induced T-cell proliferation.

“Taken together, our data demonstrate that lenalidomide-induced Th1 immunity in the lymph node that is associated with clinical response,” the study authors concluded.

Reference

  1. Aue G, Sun C, Liu D, et al. Activation of Th1 immunity within the tumor microenvironment is associated with clinical response to lenalidomide in chronic lymphocytic leukemia. J Immunol. 2018;201(7):1967-1974.

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