Multiple myeloma long-term survivors exhibit sustained immune alterations decades after first-line therapy

The long-term consequences of cancer and its therapy on the patients' immune system years after cancer-free survival remain poorly understood. Here, we present an in-depth characterization of the bone marrow immune ecosystem of multiple myeloma long-term survivors, from initial diagnosis up to 17 years following a single therapy line and cancer-free survival. Using comparative single-cell analyses combined with molecular, genomic, and functional approaches, we demonstrate that multiple myeloma long-term survivors exhibit pronounced alterations in their bone marrow microenvironment associated with impaired immunity. These immunological alterations were frequently linked to an inflammatory immune circuit fueled by the long-term persistence or resurgence of residual myeloma cells. Notably, even in the complete absence of any detectable residual disease for decades, sustained changes in the immune system were observed, suggesting an irreversible 'immunological scarring' caused by the initial exposure to the cancer and therapy. Collectively, our study provides key insights into the molecular and cellular bone marrow ecosystem of long-term survivors of multiple myeloma, revealing both reversible and irreversible alterations in the immune compartment.

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Publication Details

Journal
Nature Communications
Published
2024-11-29
DOI
https://doi.org/10.1038/s41467-024-54543-0
Citations
11
Primary Topic
Multiple Myeloma Research and Treatments
Type
article
Field-Weighted Citation Impact
5.00
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article

Multiple myeloma long-term survivors exhibit sustained immune alterations decades after first-line therapy

Daniel Hübschmann, Charles D. Imbusch, Claudia Wickenhauser, Llorenç Solé‐Boldo et al.
11 citations
Nature Communications
Multiple Myeloma Research and Treatments
5.00
article

Multiple myeloma long-term survivors exhibit sustained immune alterations decades after first-line therapy

Daniel Hübschmann, Charles D. Imbusch, Claudia Wickenhauser, Llorenç Solé‐Boldo, Brian G.M. Durie, Schayan Yousefian, Carsten Müller‐Tidow, Lea Jopp‐Saile, Simon Haas, Simon Steiger, Niklas Beumer, Malte Simon, Florian Grünschläger, Niels Weinhold, Hartmut Goldschmidt, Benedikt Brors, Mohamed H.S. Awwad, Marcus Bauer, Karsten Rippe, Marc S. Raab, Nina Prokoph, Dominik Vonficht, Tobias Boch, Raphael Lutz, Andreas Trumpp, Michael Hundemer, Patrick Stelmach, Georg Steinbuß, Anastasia Sedlmeier, Marc-Andrea Baertsch, Bogdan Avanesyan
article en
11 citations

Abstract

The long-term consequences of cancer and its therapy on the patients' immune system years after cancer-free survival remain poorly understood. Here, we present an in-depth characterization of the bone marrow immune ecosystem of multiple myeloma long-term survivors, from initial diagnosis up to 17 years following a single therapy line and cancer-free survival. Using comparative single-cell analyses combined with molecular, genomic, and functional approaches, we demonstrate that multiple myeloma long-term survivors exhibit pronounced alterations in their bone marrow microenvironment associated with impaired immunity. These immunological alterations were frequently linked to an inflammatory immune circuit fueled by the long-term persistence or resurgence of residual myeloma cells. Notably, even in the complete absence of any detectable residual disease for decades, sustained changes in the immune system were observed, suggesting an irreversible 'immunological scarring' caused by the initial exposure to the cancer and therapy. Collectively, our study provides key insights into the molecular and cellular bone marrow ecosystem of long-term survivors of multiple myeloma, revealing both reversible and irreversible alterations in the immune compartment.

Nature CommunicationsVol. 15(1)
Cedars-Sinai Medical Center (US), Queen Mary University of London (GB), German Cancer Research Center (DE), Johannes Gutenberg University Mainz (DE), Max Delbrück Center (DE), Heidelberg University (DE), University Hospital Heidelberg (DE), Leibniz Association (DE), University Medical Center of the Johannes Gutenberg University Mainz (DE), National Center for Tumor Diseases (DE), Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE), DKFZ-ZMBH Alliance (DE), Heidelberg Institute for Stem Cell Technology and Experimental Medicine (DE), University Medical Centre Mannheim (DE), Leibniz Institute for Immunotherapy, Martin Luther University Halle-Wittenberg (DE), Charité - Universitätsmedizin Berlin (DE)
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Multiple Myeloma Research and Treatments
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