Journal
EUROPEAN JOURNAL OF HAEMATOLOGY
Volume 101, Issue 1, Pages 68-77Publisher
WILEY
DOI: 10.1111/ejh.13065
Keywords
chronic lymphocytic leukemia; dendritic cell vaccination; immunotherapy; lenalidomide
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Funding
- Swedish Cancer Society
- Cancer Society in Stockholm
- King Gustav V Jubilee Fund
- Cancer and Allergy Foundation
- StratCan Karolinska Institutet
- Karolinska Institutet Foundations
- Stockholm County Council
- AFA Insurance
- Swedish Society of Medicine
- Celgene Inc.
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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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