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

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

in 45/22 / 45/23 / 631/67/1990 / 631/67/1990/804 / 631/67/69 / 692/4028/67/1059 / Adult / Aged / Aged, 80 and over / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Autografts / Cancer / Chemotherapy / DNA (Cytosine-5-)-Methyltransferases - genetics / DNA-Binding Proteins - genetics / Female / Health risk assessment / Hematology / Hematopoiesis / Hematopoiesis - genetics / Hematopoietic Stem Cell Transplantation - methods / Human health and pathology / Humanities and Social Sciences / Humans / Immunomodulation / Immunomodulators / Life Sciences / Maintenance / Male / Middle Aged / multidisciplinary / Multiple myeloma / Multiple Myeloma - genetics / Multiple Myeloma - therapy / Mutation / p53 Protein / Peripheral blood / Progression-Free Survival / Proto-Oncogene Proteins - genetics / Science / Science (multidisciplinary) / Stem cell transplantation / Stem cells / Survival / Transplantation, Autologous / Tumor Suppressor Protein p53 - genetics / Tumors / Young Adult

2020

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2020

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2020

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Journal Article

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

Sperling, Adam S.,

Keats, Jonathan J.,

Anderson, Kenneth C.,

Ebert, Benjamin L.,

Munshi, Nikhil C.,

Huynh, Daisy,

Redd, Robert,

Tahri, Sabrin,

Nassar, Amin H.,

Reardon, Brendan,

Capelletti, Marzia,

Ritz, Jerome,

Trippa, Lorenzo,

Auclair, Daniel,

Neuberg, Donna S.,

Van Allen, Eliezer M.,

Park, Jihye,

Sklavenitis-Pistofidis, Romanos,

Gibson, Christopher J.,

Bustoros, Mark,

Stewart, Chip,

Itani, Muhieddine M.,

Liu, Chia-Jen,

Richardson, Paul G.,

Laubach, Jacob P.,

AlDubayan, Saud H.,

Mehr, Shaadi,

Boehner, Cody J.,

Leventhal, Matthew,

Manier, Salomon,

Dumke, Henry,

Schlossman, Robert L.,

Soiffer, Robert J.,

Hornburg, Kalvis,

Steensma, David P.,

Ghobrial, Irene M.,

Mouhieddine, Tarek H.,

Getz, Gad

2020

Overview

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 < 0.001) due to an increase in MM progression. Multiple myeloma (MM) is treated with induction chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. Here, the authors show that the presence of clonal haematopoiesis of indeterminate potential (CHIP) at time of ASCT is associated with adverse outcomes in MM patients.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ 45/23

/ Adult