Mouhieddine TH*, Sperling AS, Redd R, Park J,
Leventhal M, Gibson CJ, Manier S, Nassar AH, Capelletti M, Huynh D, Bustoros M,
Sklavenitis-Pistofidis R, Tahri S, Hornburg K, Dumke H, Itani MM, Boehner CJ, Liu CJ, AlDubayan SH, Reardon B, Van Allen EM, Keats JJ,
Stewart C, Mehr S, Auclair D, Schlossman RL, Munshi NC, Anderson KC, Steensma DP, Laubach JP, Richardson PG, Ritz J, Ebert BL, Soiffer RJ, Trippa L,
Getz G, Neuberg DS
#, Ghobrial IM
#^
Nature Communications
11
:2996
(2020)
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.