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Multiple myeloma, gammopathies

Improving prognostic assignment in older adults with multiple myeloma using acquired genetic features, clonal hemopoiesis and telomere length

Leukemia volume 36, pages 221–224 (2022)Cite this article

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There are over 120,000 newly diagnosed Multiple myeloma (NDMM) patients annually world-wide.1 The median age at onset is 69 years, including 34.8% diagnosed above the age 75, and 9.6% above 85 years.2,3,4 Acquired genetic alterations explain some of the variability in clinical outcome but only a limited number of studies have investigated older populations where they may help refine therapeutic decision making. In this study, we have used a set of whole genome sequencing from 980 cases (Supplementary Fig. 1) entered into the CoMMpass study to identify mutational load, mutation spectrum and mutation signature together with structural variants, clonal hematopoiesis and telomere length with the aim of characterizing the contribution of these features to outcome in elderly MM patients. We show that biological aspects of the aging process, such as telomere attrition and mutagenesis, play an important role in the pathogenesis of MM and may be used to improve clinical decision making in older patients.

This dataset was comparable with previously published datasets in terms of clinical characteristics and outcome. The median age at diagnosis was 63 (range 27–93) with 43% being aged 65 or over, 13% 75 or over and 2% 85 or over, Supplementary Table 1 and Supplementary Fig. 2. We determined the impact of age on the distribution of major cytogenetic and clinical risk factors using age as a continuous variable. We did not identify a difference in the frequency of t(4;14), del(17p), gain(1q), del(1p), and ISS. However, the proportion of patients with poor ECOG performance status and higher levels of ISS increased with older age, Supplementary Fig. 3. We assessed mutational burden and mutational processes and did not identify a significant correlation between the proportion of APOBEC (SBS2 and 13) and clock-like (SBS1 and SBS5) signatures and age. We did, however, identify variation in mutation frequency with age showing that DNAH5 mutations (Corr = 0.10, BF = 3.9), KMT2B mutations (Corr = 0.1, BF = 2.4), del(6q) (Corr = 0.1, BF = 2) and del(1p) (Corr = 0.11, BF = 5.2) had a significant  but small decrease in frequency with increasing age. Interestingly, we identified a significant increase in the proportion of cases with chromothripsis as a function of increasing age (χ2 = 10, p = 0.001), with the group aged 65 and over having a frequency of 30%, Supplementary Fig. 4.

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Fig. 1: The outcome of a range of molecular and clinical features as a function of age.
Fig. 2: The distribution and nature of the mutations used to define clonal hematopoiesis.

References

  1. Myeloma - Cancer Stat Facts. SEER. https://seer.cancer.gov/statfacts/html/mulmy.html. Accessed 7 Aug 2020.

  2. Ageing Europe—2019 edition. https://ec.europa.eu/eurostat/web/products-statistical-books/-/KS-02-19-681. Accessed 7 Aug 2020.

  3. Population Projections. https://www.census.gov/programs-surveys/popproj.html. Accessed 7 Aug 2020.

  4. Home—Office for National Statistics. https://www.ons.gov.uk/. Accessed 7 Aug 2020.

  5. Mouhieddine TH, Sperling AS, Redd R, Park J, Leventhal M, Gibson CJ, et al. Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant. Nat Commun. 2020;11:2996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rustad EH, Yellapantula V, Leongamornlert D, Bolli N, Ledergor G, Nadeu F, et al. Timing the initiation of multiple myeloma. Nat Commun. 2020;11:1917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank all the patients and their families for their contributions to this study. The authors acknowledge continued support from Multiple Myeloma Research Foundation and the Perelman Family Foundation. BAW and GJM received grant support through a Translational Research Program award from the Leukemia & Lymphoma Society (6020-20). EMB received funding from the Fédération Française de Recherche sur le Myélome et les Gammapathies under the aegis of the Fondation de France.

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Author notes

  1. These authors contributed equally: Eileen M. Boyle, Louis Williams.

Authors and Affiliations

  1. Myeloma Research Program, Perlmutter Cancer Center, NYU Langone Medical Center, New-York, NY, USA

    Eileen M. Boyle, Louis Williams, Patrick Blaney, Hussein Ghamlouch, Jinyoung Choi, Yubao Wang, Jessica Caro, James H. Stoeckle, Arnaldo Arbini, David Kaminetzky, Marc Braunstein, Benedetto Bruno, Beatrice Razzo, Faith E. Davies & Gareth J. Morgan

  2. Department of Biomedical Informatics, UAMS, Little Rock, AR, USA

    Cody Ashby & Michael Bauer

  3. Division of Hematology Oncology, Indiana University, Indianapolis, IN, USA

    Brian A. Walker

  4. INSERM 1052/CNRS 5286 Cancer Research Center of Lyon, Lyon, France

    Emeline Perrial

  5. Myeloma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Benjamin Diamond, Kylee Maclachlan & Francesco Maura

  6. Myeloma Program, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA

    Ola Landgren

  7. Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Rachel Litke

  8. School of Medicine Cardiff University, Cardiff, Wales, United Kingdom

    Christopher D. Fegan

  9. Multiple Myeloma Research Laboratory, TGen, Phoenix, AZ, USA

    Johnathan Keats

  10. MMRF, Norwalk, CT, USA

    Daniel Auclair

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  1. Eileen M. Boyle
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Correspondence to Gareth J. Morgan.

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Boyle, E.M., Williams, L., Blaney, P. et al. Improving prognostic assignment in older adults with multiple myeloma using acquired genetic features, clonal hemopoiesis and telomere length. Leukemia 36, 221–224 (2022). https://doi.org/10.1038/s41375-021-01320-3

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