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

Marzia Palma, Lotta Hansson, Tom A. Mulder, Lars Adamson, Barbro Näsman-Glaser, Ingrid Eriksson, Kia Heimersson, Harriet Ryblom, Fariba Mozaffari, Ann Svensson, Giusy Gentilcore, Anders Österborg, Håkan Mellstedt

Research output: Contribution to journalArticle

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Abstract

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-γ 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.

Original languageEnglish
JournalEuropean Journal of Haematology
DOIs
Publication statusAccepted/In press - 1 Jan 2018

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B-Cell Chronic Lymphocytic Leukemia
Dendritic Cells
Vaccines
Granulocyte-Macrophage Colony-Stimulating Factor
T-Lymphocytes
Enzyme-Linked Immunospot Assay
Immunologic Monitoring
Autoimmune Hemolytic Anemia
Neoplasms
Cancer Vaccines
Cyclophosphamide
lenalidomide
Immunity
Immunization
Flow Cytometry
Vaccination
Safety
Pharmaceutical Preparations

Keywords

  • Chronic lymphocytic leukemia
  • Dendritic cell vaccination
  • Immunotherapy
  • Lenalidomide

ASJC Scopus subject areas

  • Hematology

Cite this

Palma, M., Hansson, L., Mulder, T. A., Adamson, L., Näsman-Glaser, B., Eriksson, I., ... Mellstedt, H. (Accepted/In press). Lenalidomide as immune adjuvant to a dendritic cell vaccine in chronic lymphocytic leukemia patients. European Journal of Haematology. https://doi.org/10.1111/ejh.13065

Lenalidomide as immune adjuvant to a dendritic cell vaccine in chronic lymphocytic leukemia patients. / Palma, Marzia; Hansson, Lotta; Mulder, Tom A.; Adamson, Lars; Näsman-Glaser, Barbro; Eriksson, Ingrid; Heimersson, Kia; Ryblom, Harriet; Mozaffari, Fariba; Svensson, Ann; Gentilcore, Giusy; Österborg, Anders; Mellstedt, Håkan.

In: European Journal of Haematology, 01.01.2018.

Research output: Contribution to journalArticle

Palma, M, Hansson, L, Mulder, TA, Adamson, L, Näsman-Glaser, B, Eriksson, I, Heimersson, K, Ryblom, H, Mozaffari, F, Svensson, A, Gentilcore, G, Österborg, A & Mellstedt, H 2018, 'Lenalidomide as immune adjuvant to a dendritic cell vaccine in chronic lymphocytic leukemia patients', European Journal of Haematology. https://doi.org/10.1111/ejh.13065
Palma, Marzia ; Hansson, Lotta ; Mulder, Tom A. ; Adamson, Lars ; Näsman-Glaser, Barbro ; Eriksson, Ingrid ; Heimersson, Kia ; Ryblom, Harriet ; Mozaffari, Fariba ; Svensson, Ann ; Gentilcore, Giusy ; Österborg, Anders ; Mellstedt, Håkan. / Lenalidomide as immune adjuvant to a dendritic cell vaccine in chronic lymphocytic leukemia patients. In: European Journal of Haematology. 2018.
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abstract = "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-γ 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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AU - Hansson, Lotta

AU - Mulder, Tom A.

AU - Adamson, Lars

AU - Näsman-Glaser, Barbro

AU - Eriksson, Ingrid

AU - Heimersson, Kia

AU - Ryblom, Harriet

AU - Mozaffari, Fariba

AU - Svensson, Ann

AU - Gentilcore, Giusy

AU - Österborg, Anders

AU - Mellstedt, Håkan

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N2 - 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-γ 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.

AB - 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-γ 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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KW - Dendritic cell vaccination

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