4.2 Article

Lenalidomide as immune adjuvant to a dendritic cell vaccine in chronic lymphocytic leukemia patients

期刊

EUROPEAN JOURNAL OF HAEMATOLOGY
卷 101, 期 1, 页码 68-77

出版社

WILEY
DOI: 10.1111/ejh.13065

关键词

chronic lymphocytic leukemia; dendritic cell vaccination; immunotherapy; lenalidomide

资金

  1. Swedish Cancer Society
  2. Cancer Society in Stockholm
  3. King Gustav V Jubilee Fund
  4. Cancer and Allergy Foundation
  5. StratCan Karolinska Institutet
  6. Karolinska Institutet Foundations
  7. Stockholm County Council
  8. AFA Insurance
  9. Swedish Society of Medicine
  10. Celgene Inc.

向作者/读者索取更多资源

Objectives We previously showed that immunization with ex vivo-generated autologous dendritic cells loaded with apoptotic tumor cells (Apo-DC) potentiated tumor-specific immunity in chronic lymphocytic leukemia (CLL) patients. Here, we evaluated safety and immunogenicity of Apo-DC in combination with lenalidomide, granulocyte-macrophage colony-stimulating factor (GM-CSF), and low-dose cyclophosphamide (CTX). Methods Ten previously untreated patients with slowly progressing CLL received 5 Apo-DC vaccinations and lenalidomide orally for 24 weeks either alone (cohort I, n = 5) or together with subcutaneous GM-CSF and intravenous CTX (cohort II, n = 5). Tumor-specific T-cell responses were measured by proliferation and IFN-gamma ELISPOT assays. Immune monitoring was performed by flow cytometry. Results Dose-limiting toxicity was observed in 3/10 patients, 2 in cohort I and one in cohort II. One patient developed autoimmune hemolytic anemia and another grade 4 thrombocytopenia. Vaccine-induced immune responses were seen in 5/5 and 4/5 patients in cohort I and II, respectively. The expression of immune checkpoints on T cells did not change significantly. Conclusions Lenalidomide alone or in combination with GM-CSF and low-dose CTX as immune adjuvant to the Apo-DC vaccine elicited tumor-specific T-cell responses in CLL patients. However, unexpected toxicity was observed and caution is suggested in further exploring this drug as immune adjuvant in CLL.

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