Bone marrow immune cell composition reflects multiple myeloma progression and affects treatment response
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.
Authors
- Emilia Gigliotta (ORCID: https://orcid.org/0009-0007-2070-0652)
- Francesco Dieli (ORCID: https://orcid.org/0000-0002-6685-352X)
- Francesca Garofano (ORCID: https://orcid.org/0009-0005-4698-0264)
- Cirino Botta (ORCID: https://orcid.org/0000-0002-1522-4504)
- Michele Cea (ORCID: https://orcid.org/0000-0002-1530-6729)
- Elena Bestoso
- Mojtaba Shekarkar Azgomi (ORCID: https://orcid.org/0000-0002-0642-0431)
- Alessandro Gozzetti (ORCID: https://orcid.org/0000-0003-0769-6891)
- Donatella Raspadori (ORCID: https://orcid.org/0000-0002-2597-6312)
- Anna Maria Corsale (ORCID: https://orcid.org/0000-0002-2541-4619)
- Serena Meraviglia (ORCID: https://orcid.org/0000-0002-0383-5818)
- Marta Di Simone (ORCID: https://orcid.org/0000-0003-1973-0540)
- Antonio Giovanni Solimando (ORCID: https://orcid.org/0000-0002-2293-9698)
- Renato Zambello (ORCID: https://orcid.org/0000-0002-8799-5324)
- Andreas Beilhack (ORCID: https://orcid.org/0000-0002-3165-2648)
- Federica Cioffi (ORCID: https://orcid.org/0000-0002-1530-8556)
- Maria Speciale (ORCID: https://orcid.org/0000-0001-8251-7537)
- Francesca M. Buffa (ORCID: https://orcid.org/0000-0003-0409-406X)
- Paula Tabares (ORCID: https://orcid.org/0000-0003-0401-1711)
- Paola Pacelli (ORCID: https://orcid.org/0000-0001-5838-1123)
- Sergio Siragusa (ORCID: https://orcid.org/0000-0002-1641-6508)
- Nadia Caccamo (ORCID: https://orcid.org/0000-0002-1018-5710)
- Giusy Corsale
- C. Aquilina
- Miriam Sciortino
- Fulvio Brucato
- Marta Biondo
Institutions
- University of Siena (IT)
- University of Padua (IT)
- University of Catania (IT)
- Ospedale Santa Maria alle Scotte (IT)
- Universitätsklinikum Würzburg (DE)
- Azienda Ospedaliera Universitaria Senese (IT)
- Ospedale Policlinico San Martino (IT)
- University of Bari Aldo Moro (IT)
- University of Palermo (IT)
Publication Details
- Journal
- Blood Neoplasia
- Published
- 2025-10-17
- DOI
- https://doi.org/10.1016/j.bneo.2025.100174
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00