title: Lenalidomide enhances myeloma-specific T-cell responses in vivo and in vitro.
abstract: Immunomodulation is an important part of lenalidomide's mode of action. We analyzed the impact of lenalidomide on T cells from patients with multiple myeloma during lenalidomide therapy in vivo and in patients with lenalidomide-refractory disease in vitro Patients enrolled in the German Speaking Myeloma Multicenter Group (GMMG) MM5 trial received a consolidation therapy with two cycles of lenalidomide after autologous stem cell transplantation (ASCT). Half of the study population continued treatment with lenalidomide maintenance therapy for 2 y, while the other patients received lenalidomide maintenance therapy until complete remission. We analyzed 58 patients with (n = 30) or without (n = 28) lenalidomide therapy and 12 patients refractory to lenalidomide with regards to their anti-myeloma-specific T-cell responses displayed by IFNγ, Granzyme B, and Perforin secretion. The immunophenotype of T-cells was investigated by flow cytometry. Significantly, more myeloma-specific T-cell responses were observed in patients during lenalidomide therapy, compared to patients without treatment. Furthermore, we found on T-cells from patients treated with lenalidomide a decreased CD45RA expression, indicating a maturated immunophenotype and a decreased expression of CD57, indicating functional T cells. An improved myeloma-specific T-cell response was observed in 6 out of 12 heavily pretreated patients (refractory to lenalidomide) after in vitro incubation with lenalidomide. Complementary to the results in vivo, lenalidomide decreased CD45RA expression on T cells in vitro.
authors.affiliation: Department of Internal Medicine V, University of Heidelberg , Heidelberg, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Krämer
authors.affiliation: Department of Internal Medicine V, University of Heidelberg , Heidelberg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Engelhardt
authors.affiliation: Department of Internal Medicine V, University of Heidelberg , Heidelberg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fichtner
authors.affiliation: Department of Internal Medicine V, University of Heidelberg , Heidelberg, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Neuber
authors.affiliation: Department of Internal Medicine V, University of Heidelberg , Heidelberg, Germany.
authors.forename: Sergej
authors.initials: S
authors.lastname: Medenhoff
authors.affiliation: Department of Internal Medicine V, University of Heidelberg , Heidelberg, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Bertsch
authors.affiliation: Department of Internal Medicine V, University of Heidelberg , Heidelberg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Hillengass
authors.affiliation: Department of Internal Medicine V, University of Heidelberg , Heidelberg, Germany.
authors.forename: Marc-Steffen
authors.initials: MS
authors.lastname: Raab
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany; National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.affiliation: Department of Internal Medicine V, University of Heidelberg , Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany; National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.affiliation: Department of Internal Medicine V, University of Heidelberg , Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hundemer
keywords: Antigen-specific T-cells; CD45RA; CD57; immunotherapy; lenalidomide; multiple myeloma