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

Journal article

R. Lutz, F. Grünschläger, Malte Simon, M. Awwad, M. Bauer, S. Yousefian, N. Beumer, L. Jopp-Saile, Anastasia Sedlmeier, Llorenç Solé-Boldo, Bogdan Avanesyan, Dominik Vonficht, Patrick Stelmach, Georg Steinbuss, T. Boch, Simon Steiger, M. Baertsch, Nina Prokoph, K. Rippe, B. Durie, Claudia Wickenhauser, A. Trumpp, Carsten Müller-Tidow, D. Huebschmann, Niels Weinhold, M. Raab, B. Brors, Hartmut Goldschmidt, Charles D. Imbusch, M. Hundemer, Simon Haas
Nature Communications, 2024

Semantic Scholar DOI PubMedCentral PubMed

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APA Click to copy
Lutz, R., Grünschläger, F., Simon, M., Awwad, M., Bauer, M., Yousefian, S., … Haas, S. (2024). Multiple myeloma long-term survivors exhibit sustained immune alterations decades after first-line therapy. Nature Communications.

Chicago/Turabian Click to copy
Lutz, R., F. Grünschläger, Malte Simon, M. Awwad, M. Bauer, S. Yousefian, N. Beumer, et al. “Multiple Myeloma Long-Term Survivors Exhibit Sustained Immune Alterations Decades after First-Line Therapy.” Nature Communications (2024).

MLA Click to copy
Lutz, R., et al. “Multiple Myeloma Long-Term Survivors Exhibit Sustained Immune Alterations Decades after First-Line Therapy.” Nature Communications, 2024.

BibTeX Click to copy

@article{r2024a,
  title = {Multiple myeloma long-term survivors exhibit sustained immune alterations decades after first-line therapy},
  year = {2024},
  journal = {Nature Communications},
  author = {Lutz, R. and Grünschläger, F. and Simon, Malte and Awwad, M. and Bauer, M. and Yousefian, S. and Beumer, N. and Jopp-Saile, L. and Sedlmeier, Anastasia and Solé-Boldo, Llorenç and Avanesyan, Bogdan and Vonficht, Dominik and Stelmach, Patrick and Steinbuss, Georg and Boch, T. and Steiger, Simon and Baertsch, M. and Prokoph, Nina and Rippe, K. and Durie, B. and Wickenhauser, Claudia and Trumpp, A. and Müller-Tidow, Carsten and Huebschmann, D. and Weinhold, Niels and Raab, M. and Brors, B. and Goldschmidt, Hartmut and Imbusch, Charles D. and Hundemer, M. and Haas, Simon}
}

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.