Measurable residual mutated IDH2 before allogeneic transplant for acute myeloid leukemia

Routine genetic profiling of acute myeloid leukemia (AML) at initial diagnosis has allowed subgroup specific prognostication, drug development, and clinical management strategies. The optimal approach for treatment response assessment for AML subgroups has not yet however been determined. A nationwide cohort of 257 adult patients in first remission (CR1) from AML associated with an IDH2 mutation (IDH2m) undergoing allogeneic transplant during the period 2013-2019 in the United States had rates of relapse and survival three years after transplantation of 24% and 71%, respectively. Pre-transplant clinical flow cytometry assessment was not useful in stratifying patients based on risk of post-transplant relapse or death. DNA-sequencing was performed on CR1 blood collected within 100 days before transplant. Persistent detection of IDH2m was common (51%) and associated with increased relapse and death compared to testing negative. Co-mutation at initial diagnosis with mutated NPM1 and/or FLT3-ITD was common in this cohort (41%) and use of these validated MRD markers provided superior stratification compared to IDH2m testing. Patients testing negative for IDH2m prior to transplant had low relapse-related death, regardless of conditioning intensity. Post-transplant relapse rates for those with persistently detectable IDH2m in pre-transplant remission were lower after the FDA approval of enasidenib in August 2017.

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Publication Details

Journal
Bone Marrow Transplantation
Published
2024-10-25
DOI
https://doi.org/10.1038/s41409-024-02449-2
Citations
8
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
3.64

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article

Measurable residual mutated IDH2 before allogeneic transplant for acute myeloid leukemia

Scott L. Zeger, Niveditha Ravindra, Steven M. Devine, Kristin Page et al.
8 citations
Bone Marrow Transplantation
Acute Myeloid Leukemia Research
3.64
article

Measurable residual mutated IDH2 before allogeneic transplant for acute myeloid leukemia

Scott L. Zeger, Niveditha Ravindra, Steven M. Devine, Kristin Page, Antonio Jiménez, Zoë C. Wong, Pranay S. Hegde, Yi‐Bin Chen, Marcos de Lima, Devdeep Mukherjee, Evan Chris Chen, Firas El Chaer, Georgia Andrew, Gege Gui, Laura W. Dillon, Wael Saber, Christopher Simon Hourigan, Stephen R. Spellman, Partow Kebriaei, Sunil Iyer, Mark Robert Litzow, Jeffery J. Auletta, Adam Corner
article en
8 citations

Abstract

Routine genetic profiling of acute myeloid leukemia (AML) at initial diagnosis has allowed subgroup specific prognostication, drug development, and clinical management strategies. The optimal approach for treatment response assessment for AML subgroups has not yet however been determined. A nationwide cohort of 257 adult patients in first remission (CR1) from AML associated with an IDH2 mutation (IDH2m) undergoing allogeneic transplant during the period 2013-2019 in the United States had rates of relapse and survival three years after transplantation of 24% and 71%, respectively. Pre-transplant clinical flow cytometry assessment was not useful in stratifying patients based on risk of post-transplant relapse or death. DNA-sequencing was performed on CR1 blood collected within 100 days before transplant. Persistent detection of IDH2m was common (51%) and associated with increased relapse and death compared to testing negative. Co-mutation at initial diagnosis with mutated NPM1 and/or FLT3-ITD was common in this cohort (41%) and use of these validated MRD markers provided superior stratification compared to IDH2m testing. Patients testing negative for IDH2m prior to transplant had low relapse-related death, regardless of conditioning intensity. Post-transplant relapse rates for those with persistently detectable IDH2m in pre-transplant remission were lower after the FDA approval of enasidenib in August 2017.

Bone Marrow TransplantationVol. 60(2)
National Institutes of Health (US), National Marrow Donor Program (US), Bio-Rad (United States) (US), The University of Texas MD Anderson Cancer Center (US), Johns Hopkins University (US), Medical College of Wisconsin (US), Columbia University Irving Medical Center (US), Massachusetts General Hospital (US), Institute of Cancer Research (CA), National Heart, Lung, and Blood Institute (US), Dana-Farber Cancer Institute (US), Mayo Clinic in Arizona (US), Cancer Research Center (US), Biomedical Research Institute (US), Sylvester Comprehensive Cancer Center (US), University of Virginia (US), The Ohio State University (US), Virginia Tech (US)
U.S. Department of Defense, Foundation for the National Institutes of Health, Amgen, AstraZeneca, Gilead Sciences, Takeda Pharmaceuticals U.S.A., Jazz Pharmaceuticals, Syndax Pharmaceuticals, National Institutes of Health, Health Resources and Services Administration, Genentech, U.S. Navy, National Heart, Lung, and Blood Institute, Office of Naval Research, National Cancer Institute, National Institute of Allergy and Infectious Diseases
Openalex Percentile: Top 6%
Acute Myeloid Leukemia Research
3.64
DOIOpen Access PDFOpenAlex
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