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Title: Immune status of high-risk smoldering multiple myeloma patients and its therapeutic modulation under LenDex: a longitudinal analysis.
Authors: Paiva, Bruno
Mateos, María Victoria
Sanchez-Abarca, Luis Ignacio
Puig, Noemi
Vidriales, María-Belén
López-Corral, Lucía
Corchete, Luis A
Hernandez, Miguel T
Bargay, Joan
de Arriba, Felipe
de la Rubia, Javier
Teruel, Ana-Isabel
Giraldo, Pilar
Rosiñol, Laura
Prosper, Felipe
Oriol, Albert
Hernández, José
Esteves, Graça
Lahuerta, Juan José
Bladé, Joan
Perez-Simon, Jose Antonio
San Miguel, Jesús F
Spanish Myeloma Group / Program Study and Treatment of Hematological Malignancies cooperative study groups
metadata.dc.subject.mesh: Adult
Aged, 80 and over
Biomarkers, Tumor
Cell Proliferation
Induction Chemotherapy
Killer Cells, Natural
Longitudinal Studies
Maintenance Chemotherapy
Middle Aged
Multiple Myeloma
Risk Factors
Issue Date: 14-Dec-2015
Abstract: There is significant interest in immunotherapy for the treatment of high-risk smoldering multiple myeloma (SMM), but no available data on the immune status of this particular disease stage. Such information is important to understand the interplay between immunosurveillance and disease transformation, but also to define whether patients with high-risk SMM might benefit from immunotherapy. Here, we have characterized T lymphocytes (including CD4, CD8, T-cell receptor γδ, and regulatory T cells), natural killer (NK) cells, and dendritic cells from 31 high-risk SMM patients included in the treatment arm of the QUIREDEX trial, and with longitudinal peripheral blood samples at baseline and after 3 and 9 cycles of lenalidomide plus low-dose dexamethasone (LenDex). High-risk SMM patients showed at baseline decreased expression of activation-(CD25/CD28/CD54), type 1 T helper-(CD195/interferon-γ/tumor necrosis factor-α/interleukin-2), and proliferation-related markers (CD119/CD120b) as compared with age-matched healthy individuals. However, LenDex was able to restore the normal expression levels for those markers and induced a marked shift in T-lymphocyte and NK-cell phenotype. Accordingly, high-risk SMM patients treated with LenDex showed higher numbers of functionally active T lymphocytes. Together, our results indicate that high-risk SMM patients have an impaired immune system that could be reactivated by the immunomodulatory effects of lenalidomide, even when combined with low-dose dexamethasone, and support the value of therapeutic immunomodulation to delay the progression to multiple myeloma. The QUIREDEX trial was registered to as #NCT00480363.
metadata.dc.identifier.doi: 10.1182/blood-2015-10-662320
Appears in Collections:Producción 2020

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