Immune biomarkers of increased infection risk in multiple myeloma

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 1,786 patients at various disease stages and treatment scenarios. Patients developing infection had significantly lower percentages of CD27+ B cells and CD27- NK cells, as well as increased CD27-/CD27+ T-cell ratio in bone marrow. These immune risk factors were validated in three independent datasets. 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, BCMA or GPRC5D targeted therapy were independently associated with infection incidence. All cell types detectable in 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.

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Publication Details

Journal
Blood
Published
2026-01-29
DOI
https://doi.org/10.1182/blood.2025031744
Primary Topic
Multiple Myeloma Research and Treatments
Type
article
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article

Immune biomarkers of increased infection risk in multiple myeloma

Nikolaos Tsakirakis, Febe Smits, A. Orfao, V. Cabañas et al.
Blood
Multiple Myeloma Research and Treatments
article

Immune biomarkers of increased infection risk in multiple myeloma

Nikolaos Tsakirakis, Febe Smits, A. Orfao, V. Cabañas, A. Sureda, de Arriba F, Catarina Maia, Ioannis V. Kostopoulos, Sunil Lakhwani, Albert Oriol, Cristina Encinas, Ourania Tsitsilonis, Esther González-García, A. Zabaleta, Esperanza Martín‐Sánchez, David Žihala, Isabel A. Calvo, Rafael Ríos-Tamayo, Panagiotis Bakouros, Laura Rosiñol, F Escalante, Joan Bladé, Bruno Paiva, Romanos Sklavenitis Pistofidis, M. Suzette Blanchard, Tuna Mutis, José J. Pérez, Michaela Machu, Irene Solia, Noemí Puig, Joan Bladé, Carlos Fernández de Larrea, Evangelos Terpos, Maria Teresa Cedena, Michelle P Aranha, Joaquín Martínez-López, Efstathios Kastritis, Irene M. Ghobrial, Paula Rodriguez-Otero, Tomas Jelínek, Sonja Zweegman, Cristina Moreno, Albert Pérez-Montaña, Carmen Roncal, Maria-Victoria Mateos, Enrique María M. Ocio, Estrella Carrillo-Cruz, Joan Bargay
article en

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 1,786 patients at various disease stages and treatment scenarios. Patients developing infection had significantly lower percentages of CD27+ B cells and CD27- NK cells, as well as increased CD27-/CD27+ T-cell ratio in bone marrow. These immune risk factors were validated in three independent datasets. 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, BCMA or GPRC5D targeted therapy were independently associated with infection incidence. All cell types detectable in 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.

Blood
Universidad de Cantabria (ES), University of Ostrava (CZ), National and Kapodistrian University of Athens (GR), Masaryk University (CZ), Hospital Universitario de Canarias (ES), Hospital General Universitario Gregorio Marañón (ES), Hospital Son Llatzer (ES), University Hospital Ostrava (CZ), Josep Carreras Leukaemia Research Institute (ES), Marqués de Valdecilla University Hospital (ES), Hospital Universitario 12 De Octubre (ES), University Hospital Brno (CZ), Institut Català d'Oncologia (ES), Amsterdam Neuroscience (NL), Navarre Institute of Health Research (ES), Instituto de Investigación Marqués de Valdecilla (ES), Hospital Clínic de Barcelona (ES), Hospital Universitario Virgen de las Nieves (ES), Dana-Farber Cancer Institute (US), Health Research Institute of the Balearic Islands (ES), Instituto de Investigación Biomédica de Salamanca (ES), Clinica Universidad de Navarra (ES), Centro de Investigación del Cáncer (ES), Instituto Murciano de Investigación Biosanitaria (ES), Hospital Universitario De Cabueñes (ES), Hospital Universitario Virgen de la Arrixaca (ES), Hospital Universitario Son Espases (ES), Hospital Universitario Virgen del Rocío (ES), Hospital Universitario de León (ES), Hospital Universitario Ramón y Cajal (ES), Universidad de Murcia (ES), Vrije Universiteit Amsterdam (NL), Chartered Institute of Management Accountants (GB)
Good health and well-being
Openalex Percentile: Top 77%
Multiple Myeloma Research and Treatments
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