Impact of lenalidomide maintenance on the immune environment of multiple myeloma patients with low tumor burden after autologous stem cell transplantation

Oncotarget
Karel FostierBrenda De Keersmaecker

Abstract

Lenalidomide is a potent anti-myeloma drug with immunomodulatory properties. It is increasingly used in a low-dose maintenance setting to prolong remission duration after standard treatment. Data on the in vivo effects of lenalidomide are scarce and sometimes different from the well-described in vitro effects. We therefore evaluated the numerical, phenotypical and functional impact of lenalidomide maintenance on several immune cell types in a cohort of seventeen homogeneously treated myeloma patients achieving a low residual myeloma burden after a bortezomib based-induction followed by autologous stem cell transplantation. Lenalidomide maintenance: 1) increased the fraction of naïve CD8+ T cells and several memory T-cell subsets, 2) reduced the numbers of terminal effector CD8+ T cells, 3) resulted in a higher expression of co-stimulatory molecules on resting T cells and of the inhibitory checkpoint molecules LAG-3 on CD4+ T cells and TIM-3 on CD4+ and CD8+ T cells, 4) reduced the number of TIGIT+ CD8+ T cells, 5) increased the number of regulatory T cells with a phenotype associated with strong suppressive capacity. Purified CD8+ T cells showed increased and more polyfunctional recall viral responses. However, PBMC responses w...Continue Reading

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Citations

Mar 13, 2020·Expert Review of Hematology·Sonia MorèMassimo Offidani
Feb 10, 2021·International Journal of Hematology·Kenji NozakiHirohiko Shibayama
Feb 2, 2021·Pigment Cell & Melanoma Research·Naveed PervaizRavinder Kumar
Mar 19, 2021·Expert Review of Hematology·Michel DelforgeNicolas Kint
Mar 23, 2021·Frontiers in Immunology·Criselle D'SouzaPaul J Neeson
Oct 12, 2021·Transplantation and Cellular Therapy·Murali JanakiramJeffrey S Miller

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Methods Mentioned

BETA
ISS
flow cytometry
leukapheresis
FACS

Software Mentioned

GraphPad Prism
FlowJo

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