title: Immune status of high-risk smoldering multiple myeloma patients and its therapeutic modulation under LenDex: a longitudinal analysis.
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 www.clinicaltrials.gov as #NCT00480363.
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain;
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.affiliation: Hospital Universitario de Salamanca, Instituto de Investigaion Biomedica de Salamanca, Instituto de Biología Molecular y Celular del Cancer (Universidad de Salamanca Centro de Investigación del Cáncer), Salamanca, Spain;
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Hospital Universitario de Salamanca, Instituto de Investigaion Biomedica de Salamanca, Instituto de Biología Molecular y Celular del Cancer (Universidad de Salamanca Centro de Investigación del Cáncer), Salamanca, Spain;
authors.forename: Luis Ignacio
authors.initials: LI
authors.lastname: Sanchez-Abarca
authors.affiliation: Hospital Universitario de Salamanca, Instituto de Investigaion Biomedica de Salamanca, Instituto de Biología Molecular y Celular del Cancer (Universidad de Salamanca Centro de Investigación del Cáncer), Salamanca, Spain;
authors.forename: Noemi
authors.initials: N
authors.lastname: Puig
authors.affiliation: Hospital Universitario de Salamanca, Instituto de Investigaion Biomedica de Salamanca, Instituto de Biología Molecular y Celular del Cancer (Universidad de Salamanca Centro de Investigación del Cáncer), Salamanca, Spain;
authors.forename: María-Belén
authors.initials: MB
authors.lastname: Vidriales
authors.affiliation: Hospital Universitario de Salamanca, Instituto de Investigaion Biomedica de Salamanca, Instituto de Biología Molecular y Celular del Cancer (Universidad de Salamanca Centro de Investigación del Cáncer), Salamanca, Spain;
authors.forename: Lucía
authors.initials: L
authors.lastname: López-Corral
authors.affiliation: Hospital Universitario de Salamanca, Instituto de Investigaion Biomedica de Salamanca, Instituto de Biología Molecular y Celular del Cancer (Universidad de Salamanca Centro de Investigación del Cáncer), Salamanca, Spain;
authors.forename: Luis A
authors.initials: LA
authors.lastname: Corchete
authors.affiliation: Hospital Universitario de Canarias, Tenerife, Spain;
authors.forename: Miguel T
authors.initials: MT
authors.lastname: Hernandez
authors.affiliation: Hospital Sont Llatzer, Palma de Mallorca, Spain;
authors.forename: Joan
authors.initials: J
authors.lastname: Bargay
authors.affiliation: Hospital Morales Messeguer, Murcia, Spain;
authors.forename: Felipe
authors.initials: F
authors.lastname: de Arriba
authors.affiliation: Hospital Universitario La Fe, Valencia, Spain;
authors.forename: Javier
authors.initials: J
authors.lastname: de la Rubia
authors.affiliation: Hospital Universitario de Valencia, Valencia, Spain;
authors.forename: Ana-Isabel
authors.initials: AI
authors.lastname: Teruel
authors.affiliation: Hospital Miguel Servet, Health Research Institute Aragón, Centro de Investigación Biomédica en Red Enfermedades Raras, Zaragoza, Spain;
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
authors.affiliation: Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain;
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain;
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
authors.affiliation: Hospital Universitari Germans Trias i Pujol, Badalona, Spain;
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Hospital General de Segovia, Segovia, Spain;
authors.forename: José
authors.initials: J
authors.lastname: Hernández
authors.affiliation: Hospital de Santa María, Lisboa, Portugal;
authors.forename: Graça
authors.initials: G
authors.lastname: Esteves
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain; and.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lahuerta
authors.affiliation: Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain;
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.affiliation: Hospital Virgen del Rocio, Sevilla, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Perez-Simon
authors.affiliation: Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain;
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003710:Demography; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D060828:Induction Chemotherapy; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D000077269:Lenalidomide; D008137:Longitudinal Studies; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology*; D012307:Risk Factors; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D014408:Biomarkers, Tumor; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide