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

Sep 28, 2026

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Bone marrow (BM) progression in multiple myeloma (MM) is driven by interactions between clonal plasma cells and the BM immune microenvironment. This study analyzes BM immune cell composition from premalignant stages to MM in 159 patients using FlowCT, covering MGUS, smoldering MM, and MM treated mostly with daratumumab. Immune changes include reduced granulocyte-to-lymphocyte ratios and increased T lymphocytes. Higher baseline BM GLR/GTL ratios predict longer progression-free survival, and daratumumab benefit associates with higher GTL, with autologous BM-derived granulocytes enhancing daratumumab cytotoxicity against primary autologous neoplastic plasma cells.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Key Points

Introduction

Disease progression and clinical risk models

Immune system role and study rationale

Methods and cohort overview

Immune composition changes across MM stages

Prognostic value of GLR/GTL ratios

Mechanistic role of BM-derived granulocytes in daratumumab response

REGULAR ARTICLE neoplasia Bone marrow immune cell composition reflects multiple myeloma progression and affects treatment response 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 and Cirino Botta2 1 Central Laboratory of Advanced Diagnosis and Biomedical Research, and 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; and 11 Department of Biomedicine, Neuroscience and Advanced Diagnosis, University of Palermo, Palermo, Italy Key Points • A higher GTL ratio improves daratumumab response and prolongs progression-free survival in patients with MM. • BM-derived granulocytes are involved in the therapeutic activity of daratumumab. 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 monoclonalgammopathy 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-tolymphocyte 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 inpatients 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. Submitted 1 April 2025; accepted 22 September 2025; prepublished online 16 October 2025. [https://doi.org/10.1016/j.bneo.2025.100174](https://doi.org/10.1016/j.bneo.2025.100174) . The data supporting the findings of this study are available from the corresponding authors, Cirino Botta ([cirino.botta@unipa.it](cirino.botta@unipa.it)) and Anna Maria Corsale (annamaria. [corsale@unipa.it](corsale@unipa.it)), on r

FAQs

What question does the study address about multiple myeloma progression?

The study investigates how bone marrow immune cell composition changes from premalignant stages to MM and how those immune patterns relate to daratumumab treatment response and outcomes.

How did the immune cell ratios change during disease progression?

Progression was associated with a reduction in the granulocyte-to-lymphocyte and granulocyte-to–T-lymphocyte ratios, alongside an increase in T lymphocytes.

What is the clinical significance of higher baseline GTL/GTL-related ratios?

Higher baseline BM GLR and GTL ratios were associated with extended progression-free survival, and patients with higher GTL treated with daratumumab-based regimens showed improved outcomes.

Sep 28, 2026

Uploaded by Terk