Lenalidomide enhances myeloma-specific T-cell responses in vivo and in vitro

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 Speakin...

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Main Authors: Krämer, Isabelle (Author) , Engelhardt, Melanie (Author) , Fichtner, Sabrina (Author) , Neuber, Brigitte (Author) , Medenhoff, Sergej (Author) , Bertsch, Uta (Author) , Hillengaß, Jens (Author) , Raab, Marc-Steffen (Author) , Hose, Dirk (Author) , Ho, Anthony Dick (Author) , Goldschmidt, Hartmut (Author) , Hundemer, Michael (Author)
Format: Article (Journal)
Language:English
Published: 31 May 2016
In: OncoImmunology
Year: 2016, Volume: 5, Issue: 5, Pages: 1-10
ISSN:2162-402X
DOI:10.1080/2162402X.2016.1139662
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1080/2162402X.2016.1139662
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Author Notes:Isabelle Krämer, Melanie Engelhardt, Sabrina Fichtner, Brigitte Neuber, Sergej Medenhoff, Uta Bertsch, Jens Hillengass, Marc-Steffen Raab, Dirk Hose, Anthony D. Ho, Hartmut Goldschmidt & Michael Hundemer
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Summary: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.
Item Description:Gesehen am 26.05.2020
Physical Description:Online Resource
ISSN:2162-402X
DOI:10.1080/2162402X.2016.1139662