Bone marrow immune cell composition reflects multiple myeloma progression and affects treatment response

  • Blood Neoplasia. 2025 Oct 16;3(1):100174. doi: 10.1016/j.bneo.2025.100174.
Anna Maria Corsale  1  2 ,  Mojtaba Shekarkar Azgomi  1 ,  Emilia Gigliotta  2 ,  Marta Di Simone  1  2 ,  Paola Pacelli  3 ,  Francesca Cioffi  2 ,  Elena Bestoso  4 ,  Donatella Raspadori  4 ,  Alessandro Gozzetti  3 ,  Antonio Solimando  5 ,  Paula Tabares  6  7 ,  Andreas Beilhack  6  7 ,  Maria Speciale  2 ,  Giusy Corsale  2 ,  Miriam Sciortino  1 ,  Cristina Aquilina  2 ,  Fulvio Brucato  1 ,  Michele Cea  8 ,  Renato Zambello  9 ,  Francesca Garofano  2 ,  Marta Biondo  10 ,  Francesca Buffa  1  11 ,  Nadia Caccamo  1  11 ,  Francesco Dieli  1  11 ,  Serena Meraviglia  1  11 ,  Sergio Siragusa  2 ,  Cirino Botta  2
Affiliations
  • 1. Central Laboratory of Advanced Diagnosis and Biomedical Research, University of Palermo, Palermo, Italy.
  • 2. Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.
  • 3. Department of Medicine, Surgery and Neurosciences, University of Siena, Policlinico S. Maria alle Scotte, Siena, Italy.
  • 4. Hematology Unit, University of Siena, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
  • 5. Unit of Internal Medicine "Guido Baccelli," Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "Aldo Moro" Medical School, Bari, Italy.
  • 6. Department of Medicine II, University Hospital of Würzburg, Würzburg, Germany.
  • 7. Interdisciplinary Center for Clinical Research Laboratory, University Hospital of Würzburg, Würzburg, Germany.
  • 8. Hematology Unit, Department of Internal Medicine, University of Genoa, IRCSS Ospedale Policlinico San Martino, Genova, Italy.
  • 9. Hematology Unit, Department of Medicine, University of Padova, Padua, Italy.
  • 10. Hematology Section, Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy.
  • 11. Department of Biomedicine, Neuroscience and Advanced Diagnosis, University of Palermo, Palermo, Italy.
PMID: 41480309 DOI: 10.1016/j.bneo.2025.100174
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.

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