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

Nature Communications
Tarek H MouhieddineIrene M Ghobrial

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.

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Citations

Sep 24, 2020·Cancer·Susan Bal, Luciano J Costa
Jan 5, 2021·Current Opinion in Hematology·C Matthias WilkSteffen Boettcher
Jan 6, 2021·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·Dominik C BenzSharmila Dorbala
Mar 10, 2021·Pathology·Danielle Hammond, Sanam Loghavi
Mar 19, 2021·Disease Models & Mechanisms·Paulina M Strzelecka, Frederik Damm
Jun 3, 2021·Journal of Clinical Medicine·Sarah A HolsteinPhilip L McCarthy
Jun 27, 2021·Blood Cancer Journal·Rajshekhar ChakrabortyAlok A Khorana
Aug 4, 2021·Blood Advances·Peter G MillerBenjamin L Ebert
Aug 12, 2021·Nature Communications·Oriol PichNuria Lopez-Bigas
Jul 31, 2021·Cancer Science·Shuhei Asada, Toshio Kitamura
Aug 4, 2021·Current Opinion in Hematology·Chiara ElenaLuca Malcovati
Jul 4, 2021·Leukemia·Malte von BoninMartin Bornhäuser
Aug 20, 2021·Cancer Discovery·Thomas Köhnke, Ravindra Majeti
Jan 12, 2022·American Journal of Hematology·Malgorzata K NowakowskaKevin T Nead
Jan 22, 2022·Expert Review of Clinical Pharmacology·Meghana Kesireddy, Sarah A Holstein

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Methods Mentioned

BETA
MDS
ISS

Software Mentioned

BWA
ABSOLUTE
GATK3
GATK MuTect2
Integrated Genome Viewer ( IGV )
PicardTools
Variant Effect Predictor
RealignmentFilter
Orientation
mem

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