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

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 < 0.001) due to an increase in MM progression.

SUBMITTER: Mouhieddine TH 

PROVIDER: S-EPMC7293239 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Mouhieddine Tarek H TH   Sperling Adam S AS   Redd Robert R   Park Jihye J   Leventhal Matthew M   Gibson Christopher J CJ   Manier Salomon S   Nassar Amin H AH   Capelletti Marzia M   Huynh Daisy D   Bustoros Mark M   Sklavenitis-Pistofidis Romanos R   Tahri Sabrin S   Hornburg Kalvis K   Dumke Henry H   Itani Muhieddine M MM   Boehner Cody J CJ   Liu Chia-Jen CJ   AlDubayan Saud H SH   Reardon Brendan B   Van Allen Eliezer M EM   Keats Jonathan J JJ   Stewart Chip C   Mehr Shaadi S   Auclair Daniel D   Schlossman Robert L RL   Munshi Nikhil C NC   Anderson Kenneth C KC   Steensma David P DP   Laubach Jacob P JP   Richardson Paul G PG   Ritz Jerome J   Ebert Benjamin L BL   Soiffer Robert J RJ   Trippa Lorenzo L   Getz Gad G   Neuberg Donna S DS   Ghobrial Irene M IM  

Nature communications 20200612 1

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 13  ...[more]