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Haematological cancer

From little subclones grow mighty oaks

New genetic analyses demonstrate that the presence of low-frequency subclonal populations, including high-risk subclones, at diagnosis in multiple myeloma can contribute to disease relapse and poor clinical outcomes. Thus, sensitive detection approaches are required to detect these subclones at diagnosis together with innovative treatment strategies to eradicate low-frequency, high-risk subclones and prevent them from becoming dominant.

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References

  1. Davies, F. E. et al. Perspectives on the risk-stratified treatment of multiple myeloma. Blood Cancer Discov. 3, 273–284 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Facon, T. et al. Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. Blood 131, 301–310 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Attal, M. et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N. Engl. J. Med. 376, 1311–1320 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Voorhees, P. M. et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood 136, 936–945 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jones, J. R. et al. Clonal evolution in myeloma: the impact of maintenance lenalidomide and depth of response on the genetics and sub-clonal structure of relapsed disease in uniformly treated newly diagnosed patients. Haematologica 104, 1440–1450 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Croft, J. et al. Copy number evolution and its relationship with patient outcome-an analysis of 178 matched presentation-relapse tumor pairs from the Myeloma XI trial. Leukemia 35, 2043–2053 (2021).

    Article  CAS  PubMed  Google Scholar 

  7. Lannes, R. et al. In multiple myeloma, high-risk secondary genetic events observed at relapse are present from diagnosis in tiny, undetectable subclonal populations. J. Clin. Oncol. https://doi.org/10.1200/JCO.21.01987 (2022).

    Article  PubMed  Google Scholar 

  8. Boyle, E. M. et al. BRAF and DIS3 mutations associate with adverse outcome in a long-term follow-up of patients with multiple myeloma. Clin. Cancer Res. 26, 2422–2432 (2020).

    Article  CAS  PubMed  Google Scholar 

  9. Mikulasova, A. et al. Microhomology-mediated end joining drives complex rearrangements and overexpression of MYC and PVT1 in multiple myeloma. Haematologica 105, 1055–1066 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Laks, E. et al. Clonal decomposition and DNA replication states defined by scaled single-cell genome sequencing. Cell 179, 1207–1221.e22 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Faith E. Davies.

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Competing interests

F.E.D. is an advisory board member for Abbvie, BMS/Celgene, GSK, Janssen, Oncopeptide, Regeneron, Pfizer, Sanofi and Takeda. E.M.B. declares no competing interests.

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Boyle, E.M., Davies, F.E. From little subclones grow mighty oaks. Nat Rev Clin Oncol 20, 141–142 (2023). https://doi.org/10.1038/s41571-022-00727-w

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