Bone marrow immune cell composition reflects multiple myeloma progression and affects treatment response
Year: 2025
Type: article
Study design: Observational Study
Abstract: The progression of multiple myeloma (MM) is characterized by intricate interactions between clonal plasma cells and the bone marrow (BM) microenvironment. In this study, we conducted a comprehensive analysis of BM immune cell composition spanning from premalignant stages to MM, using FlowCT, a semiautomated workspace empowered to analyze large data sets. Our cohort comprised 159 patients, covering monoclonal gammopathy of undetermined significance, smoldering MM, and MM, with most undergoing treatment with a daratumumab-based regimen. The evolving disease showed alterations in immune cell populations, including a reduction in the granulocyte-to-lymphocyte ratio (GLR) and granulocyte-to-T-lymphocyte (GTL) ratio, alongside an increase in T lymphocytes. Higher baseline levels of BM GLR and GTL ratio were associated with extended progression-free survival. Moreover, improved outcomes were observed in patients with a higher GTL ratio treated with daratumumab-based regimens. Furthermore, autologous BM-derived granulocytes enhance daratumumab-mediated cytotoxicity against primary autologous neoplastic plasma cells, unveiling a novel BM-granulocyte-dependent mechanism of action for daratumumab in patients with MM. These findings emphasize the dynamic nature of the BM immune compartment during MM progression and underscore the prognostic significance of immune cell composition in guiding therapeutic approaches and enhancing patient outcomes.
Source: Blood Neoplasia
Authors: Anna Maria Corsale, Mojtaba Shekarkar Azgomi, Emilia Gigliotta, Marta Di Simone, Paola Pacelli, Francesca Cioffi, Elena Bestoso, Donatella Raspadori, Alessandro Gozzetti, Antonio Solimando, Paula Tabares, Andreas Beilhack, Maria Speciale, Giusy Corsale, Miriam Sciortino, Cristina Aquilina, Fulvio Brucato, Michele Cea, Renato Zambello, Francesca Garofano, Marta Biondo, Francesca Buffa, Nadia Caccamo, Francesco Dieli, Serena Meraviglia, Sergio Siragusa, Cirino Botta
Institutions: University of Palermo, University of Siena, Ospedale Santa Maria alle Scotte, Azienda Ospedaliera Universitaria Senese, University of Bari Aldo Moro, University of Würzburg, Universitätsklinikum Würzburg, Ospedale Policlinico San Martino, University of Genoa, University of Padua, University of Catania
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
OpenAlex ID: W4415269583