Treatment with lenalidomide modulates T‐cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia

• Published in: Cancer Vol. 117; no. 17; pp. 3999 - 4008
• Main Authors: Lee, Bang‐Ning, Gao, Hui, Cohen, Evan N., Badoux, Xavier, Wierda, William G., Estrov, Zeev, Faderl, Stefan H., Keating, Michael J., Ferrajoli, Alessandra, Reuben, James M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2011; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Cancer; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell activation; Cell number; Chronic lymphocytic leukemia; Clinical Trials as Topic - nursing; Cytokines; Cytokines - biosynthesis; Enumeration; Female; Hematologic and hematopoietic diseases; Humans; Immunologic Factors - therapeutic use; Immunomodulation; immunomodulatory agents; Immunophenotyping; Immunoproliferative diseases; Immunotherapy; Interleukin-2 - immunology; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes; Lymphocytes T; Male; Medical sciences; Patients; Peripheral blood; Reduction; T cell receptors; T cells; T-Lymphocyte Subsets - immunology; Targeted cancer therapy; Thalidomide - analogs & derivatives; Thalidomide - therapeutic use; Tumors; Antineoplastic agent; Human; Immunophenotype; Lenalidomide; Immunomodulation; Cytokine; Malignant hemopathy; Biosynthesis; T cells; immunomodulatory agents; Chronic lymphocytic leukemia; Cancerology; Treatment; Lymphoproliferative syndrome; T-Lymphocyte; cytokines; Cancer
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.25983

BACKGROUND: Lenalidomide, an immunomodulatory agent, has activity in lymphoproliferative disorders. The authors, therefore, evaluated its effects on T‐cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia (CLL). METHODS: To study the immunomodulatory effects of lenalidomide in CLL, the authors recruited 24 patients with untreated CLL enrolled in a phase 2 clinical trial of lenalidomide and obtained peripheral blood specimens for immunologic studies consisting of enumeration of T cells and assessing their ability to synthesize cytokines after activation through T‐cell receptor (TCR). RESULTS: After 3 cycles of therapy, patients had a significant reduction in percentage (%) and absolute lymphocyte count (ALC) and an increase in percentage of T cells, percentage of activated CD8+ T cells producing IFN‐γ, and percentage of regulatory T (TR) cells when compared with their respective levels before treatment. After 15 cycles of treatment, responder patients had significant reduction in percentage of lymphocytes and ALC, percentage of activated CD4+ T cells producing IL‐2, IFN‐γ, or TNF‐α, and percentage of TR cells when compared with their perspective levels after 3 cycles of treatment. Furthermore, the numbers of activated CD4+ T cells producing IL‐2, IFN‐γ, or TNF‐α, activated CD8+ T cells producing IFN‐γ, and TR cells normalized to the range of healthy subjects. CONCLUSIONS: Treatment with lenalidomide resulted in the normalization of functional T‐cell subsets in responders, suggesting that lenalidomide may modulate cell‐mediated immunity in patients with CLL. Cancer 2011;. © 2011 American Cancer Society. Treatment with lenalidomide resulted in the normalization of functional T‐cell subsets in responders suggesting that lenalidomide may modulate cell‐mediated immunity in patients with chronic lymphocytic leukemia.