Immune biomarkers of increased infection risk in multiple myeloma
Abstract
Abstract Infection remains a leading cause of morbidity in multiple myeloma. Preventing infections is paramount and immune profiling could reflect the cumulative effect of host-, tumor-, and treatment-related immunosuppression. However, current understanding of immune dysfunction and its association with infection is limited. To address this gap in knowledge and identify immune biomarkers of increased infection risk, we performed immune profiling using next-generation flow cytometry in bone marrow and peripheral blood samples from 1786 patients at various disease stages and treatment scenarios. Patients developing infection had significantly lower percentages of CD27+ B cells and CD27− natural killer cells, as well as an increased CD27−/CD27+ T-cell ratio in the bone marrow. These immune risk factors were validated in 3 independent data sets. An immune score was developed to stratify patients with ≤1 vs ≥2 of the aforementioned risk factors, which was associated with higher infection incidence (35% vs 60%, P< .001). The immune score (odds ratio, 2.31; P< .001), disease stage, and CD38-, B-cell maturation antigen-, or G protein-coupled receptor class C group 5 member D-targeted therapy were independently associated with infection incidence. All cell types detectable in the bone marrow and peripheral blood were significantly correlated, suggesting that immune biomarkers of increased infection risk could be monitored using minimally invasive methods that are available in routine laboratories.
Article Details
Authors (49)
Aintzane Zabaleta
Cancer Center Clinica Universidad de Navarra (CCUN), Centro de Investigacion Medica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IdiSNA), CIBER-ONC number CB16/12/00369, Pamplona, Spain, Pamplona, Spain
Luis-Esteban Tamariz-Amador
Ioannis V. Kostopoulos
2Department of Biology, National and Kapodistrian University of Athens, Athens, Greece
Romanos Sklavenitis-Pistofidis
Febe Smits
6Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Paula Rodriguez-Otero
Carmen Roncal
1Cancer Center Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, CIBER-ONC number CB16/12/00369, Pamplona, Spain
Michelle P. Aranha
David Zihala
9Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
Michaela Machu
10Faculty of Medicine, Masaryk University, Brno, Czech Republic
Nikolaos Tsakirakis
2Department of Biology, National and Kapodistrian University of Athens, Athens, Greece
Panagiotis Bakouros
2Department of Biology, National and Kapodistrian University of Athens, Athens, Greece
Ourania Tsitsilonis
National and Kapodistrian University of Athens, Athens, Greece
Irene Solia
12Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
Cristina Moreno
Catarina Maia
1Cancer Center Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, CIBER-ONC number CB16/12/00369, Pamplona, Spain
Esperanza Martin-Sanchez
1Cancer Center Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, CIBER-ONC number CB16/12/00369, Pamplona, Spain
José J. Perez
13Department of Hematology, Hospital Universitario de Salamanca Hematología, Instituto de Investigación Biomédica de Salamanca, CIBER-ONC number CB16/12/00233, Salamanca, Spain
Cristina Encinas
14Department of Hematology, Hospital General Universitario Gregorio Marañón, liSGM, Madrid, Spain
Rafael Ríos-Tamayo
Hospital Universitario Virgen de las Nieves, Granada, Spain
Albert Oriol
Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Spain
María-Jesús Blanchard
Hospital Ramon y Cajal, madrid, Spain
Felipe de Arriba
18Department of Hematology, Hospital Morales Meseguer, IMIB Pascual Parrilla, Universidad de Murcia, Murcia, Spain
María-Esther Gonzalez
19Department of Hematology, Hospital Universitario Cabueñes, Gijón, Spain
Sunil Lakhwani
Hospital Universitario de Canarias. Universidad de La Laguna., San Cristobal de La Laguna, Tenerife, Spain
Anna Sureda
Institut Català d'Oncologia, Barcelona, Spain
Valentin Cabañas
21Department of Hematology, IMIB Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain
Fernando Escalante
22Department of Hematology, Complejo Hospitalario de León, León, Spain
Estrella Carrillo-Cruz
23Unidad de Gestión Clínica de Hematología, Hospital Virgen del Rocío, Instituto de Biomedicina (IBIS/CSIC/CIBERONC), Universidad de Sevilla
Albert Pérez-Montaña
24Department of Hematology, Hospital Universitario Son Espases, Palma, Spain
Enrique M. Ocio
From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) — all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) — all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary’s Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) — all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d’Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.)...
Joan Bargay
Hospital Universitario Son LLatzer, Instituto de Investigación Sanitaria Illes Balears (IdISBa),, Palma de Mallorca, Spain
Alberto Orfao
Tomas Jelinek
Department of Hemato-oncology, University Hospital Ostrava, Ostrava, Czech Republic
Irene M. Ghobrial
Tuna Mutis
6Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Sonja Zweegman
Evangelos Terpos
Efstathios Kastritis
Joaquín Martínez-López
Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre, Complutense University of Madrid, Centro Nacional de Investigaciones Oncológicas, Madrid Institute of Cancer, Madrid
Juan-Jose Lahuerta
Instituto de Investigación.Hospital Universitario 12 de Octubre, Madrid, Spain
Carlos Fernandez de Larrea
29Department of Hematology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
Laura Rosiñol
Hospital Clínic de Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona
Joan Bladé
Hospital Clínic i Provincial, Institut de Investicacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
María-Victoria Mateos
Jesus San-Miguel
Maria-Teresa Cedena
Noemi Puig
Bruno Paiva