Premium
Lenalidomide as immune adjuvant to a dendritic cell vaccine in chronic lymphocytic leukemia patients
Author(s) -
Palma Marzia,
Hansson Lotta,
Mulder Tom A.,
Adamson Lars,
NäsmanGlaser Barbro,
Eriksson Ingrid,
Heimersson Kia,
Ryblom Harriet,
Mozaffari Fariba,
Svensson Ann,
Gentilcore Giusy,
Österborg Anders,
Mellstedt Håkan
Publication year - 2018
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.13065
Subject(s) - medicine , elispot , lenalidomide , immunology , immune system , chronic lymphocytic leukemia , adjuvant , cyclophosphamide , immunogenicity , dendritic cell , immunotherapy , immunopotentiator , t cell , leukemia , chemotherapy , multiple myeloma
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 .