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

Mouhieddine, Tarek H.; Sperling, Adam S.; Redd, Robert; Park, Jihye; Leventhal, Matthew; Gibson, Christopher J.; Manier, Salomon; Nassar, Amin H.; Capelletti, Marzia; Huynh, Daisy; Bustoros, Mark; Sklavenitis-Pistofidis, Romanos; Tahri, Sabrin; Hornburg, Kalvis; Dumke, Henry; Itani, Muhieddine M.; Boehner, Cody J.; Liu, Chia-Jen; AlDubayan, Saud H.; Reardon, Brendan; Allen, Eliezer M.; Keats, Jonathan J.; Stewart, Chip; Mehr, Shaadi; Auclair, Daniel; Schlossman, Robert L.; Munshi, Nikhil C.; Anderson, Kenneth C.; Steensma, David P.; Laubach, Jacob P.; Richardson, Paul G.; Ritz, Jerome; Ebert, Benjamin L.; Soiffer, Robert J.; Trippa, Lorenzo; Getz, Gad; Neuberg, Donna S.; Ghobrial, Irene M.

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

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, Romanos Sklavenitis-Pistofidis, Sabrin Tahri, Kalvis Hornburg, Henry Dumke, Muhieddine M. Itani, Cody J. Boehner, Chia-Jen Liu, Saud H. AlDubayan, Brendan Reardon, Eliezer M. Allen, Jonathan J. Keats, Chip Stewart, Shaadi Mehr, Daniel Auclair, Robert L. Schlossman, Nikhil C. Munshi, Kenneth C. Anderson, David P. Steensma, Jacob P. Laubach, Paul G. Richardson, Jerome Ritz, Benjamin L. Ebert, Robert J. Soiffer, Lorenzo Trippa, Gad Getz, Donna S. Neuberg and Irene M. Ghobrial ()
Additional contact information
Tarek H. Mouhieddine: Dana-Farber Cancer Institute
Adam S. Sperling: Dana-Farber Cancer Institute
Robert Redd: Dana-Farber Cancer Institute
Jihye Park: Dana-Farber Cancer Institute
Matthew Leventhal: Broad Institute of MIT and Harvard
Christopher J. Gibson: Dana-Farber Cancer Institute
Salomon Manier: Dana-Farber Cancer Institute
Amin H. Nassar: Dana-Farber Cancer Institute
Marzia Capelletti: Dana-Farber Cancer Institute
Daisy Huynh: Dana-Farber Cancer Institute
Mark Bustoros: Dana-Farber Cancer Institute
Romanos Sklavenitis-Pistofidis: Dana-Farber Cancer Institute
Sabrin Tahri: Dana-Farber Cancer Institute
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
Robert J. Soiffer: Dana-Farber Cancer Institute
Lorenzo Trippa: Dana-Farber Cancer Institute
Gad Getz: Broad Institute of MIT and Harvard
Donna S. Neuberg: Dana-Farber Cancer Institute
Irene M. Ghobrial: Dana-Farber Cancer Institute

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: 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

Date: 2020
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DOI: 10.1038/s41467-020-16805-5

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