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Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant

Author

Listed:
  • Tarek H. Mouhieddine

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Adam S. Sperling

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Robert Redd

    (Dana-Farber Cancer Institute)

  • Jihye Park

    (Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard)

  • Matthew Leventhal

    (Broad Institute of MIT and Harvard)

  • Christopher J. Gibson

    (Dana-Farber Cancer Institute)

  • Salomon Manier

    (Dana-Farber Cancer Institute
    CHU, Univ. Lille
    INSERM UMR-S1172)

  • Amin H. Nassar

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital)

  • Marzia Capelletti

    (Dana-Farber Cancer Institute)

  • Daisy Huynh

    (Dana-Farber Cancer Institute)

  • Mark Bustoros

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Romanos Sklavenitis-Pistofidis

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Sabrin Tahri

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Kalvis Hornburg

    (Dana-Farber Cancer Institute)

  • Henry Dumke

    (Dana-Farber Cancer Institute)

  • Muhieddine M. Itani

    (Massachusetts General Hospital)

  • Cody J. Boehner

    (Dana-Farber Cancer Institute)

  • Chia-Jen Liu

    (Dana-Farber Cancer Institute)

  • Saud H. AlDubayan

    (Dana-Farber Cancer Institute)

  • Brendan Reardon

    (Dana-Farber Cancer Institute)

  • Eliezer M. Allen

    (Dana-Farber Cancer Institute)

  • Jonathan J. Keats

    (Integrated Cancer Genomics Division, Translational Genomics Research Institute)

  • Chip Stewart

    (Dana-Farber Cancer Institute)

  • Shaadi Mehr

    (Multiple Myeloma Research Foundation)

  • Daniel Auclair

    (Multiple Myeloma Research Foundation)

  • Robert L. Schlossman

    (Dana-Farber Cancer Institute)

  • Nikhil C. Munshi

    (Dana-Farber Cancer Institute)

  • Kenneth C. Anderson

    (Dana-Farber Cancer Institute)

  • David P. Steensma

    (Dana-Farber Cancer Institute)

  • Jacob P. Laubach

    (Dana-Farber Cancer Institute)

  • Paul G. Richardson

    (Dana-Farber Cancer Institute)

  • Jerome Ritz

    (Dana-Farber Cancer Institute)

  • Benjamin L. Ebert

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Robert J. Soiffer

    (Dana-Farber Cancer Institute)

  • Lorenzo Trippa

    (Dana-Farber Cancer Institute
    Harvard T.H. Chan School of Public Health)

  • Gad Getz

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Donna S. Neuberg

    (Dana-Farber Cancer Institute)

  • Irene M. Ghobrial

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of MIT and Harvard)

Abstract

Multiple myeloma (MM) is a plasma-cell neoplasm that is treated with high-dose chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. The presence of somatic mutations in the peripheral blood is termed clonal hematopoiesis of indeterminate potential (CHIP) and is associated with adverse outcomes. Targeted sequencing of the stem cell product from 629 MM patients treated by ASCT at the Dana-Farber Cancer Institute (2003–2011) detects CHIP in 136/629 patients (21.6%). The most commonly mutated genes are DNMT3A, TET2, TP53, ASXL1 and PPM1D. Twenty-one from fifty-six patients (3.3%) receiving first-line IMiD maintenance develop a therapy-related myeloid neoplasm (TMN). However, regardless of CHIP status, the use of IMiD maintenance associates with improved PFS and OS. In those not receiving IMiD maintenance, CHIP is associated with decreased overall survival (OS) (HR:1.34, p = 0.02) and progression free survival (PFS) (HR:1.45, p

Suggested Citation

  • Tarek H. Mouhieddine & Adam S. Sperling & Robert Redd & Jihye Park & Matthew Leventhal & Christopher J. Gibson & Salomon Manier & Amin H. Nassar & Marzia Capelletti & Daisy Huynh & Mark Bustoros & Rom, 2020. "Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16805-5
    DOI: 10.1038/s41467-020-16805-5
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    Cited by:

    1. Oriol Pich & Iker Reyes-Salazar & Abel Gonzalez-Perez & Nuria Lopez-Bigas, 2022. "Discovering the drivers of clonal hematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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