Measurable Residual IDH1 before Allogeneic Transplant for Acute Myeloid Leukemia
Gege Gui1,2, Laura W Dillon1, Niveditha Ravindra1
1Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Abstract:
Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. The persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoetic cell transplant (alloHCT) has been established as associated with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remains incompletely defined. We performed testing for residual IDH1 variants (IDH1m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1-mutated AML at a CIBMTR site between 2013-2019. No post-transplant differences were observed between those testing IDH1m positive (n=53, 36%) and negative pre-transplant (overall survival: p = 0.4; relapse: p = 0.5). For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD or increased post-transplant relapse risk.
Insights
Detecting IDH1 mutations in blood before stem cell transplant for acute myeloid leukemia (AML) does not predict relapse risk. Only NPM1 or FLT3-ITD mutations indicate higher relapse rates in AML patients.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Measurable residual disease (MRD) is a key prognostic marker in acute myeloid leukemia (AML).
- Persistence of NPM1 or FLT3-ITD mutations in CR1 blood before allogeneic stem cell transplant (alloHCT) predicts poor outcomes.
- Prognostic significance of persistent IDH1 mutations in AML patients pre-alloHCT is not well-defined.
Approach:
- Investigated the prognostic value of pre-transplant CR1 blood IDH1 mutations (IDH1m) in 148 adult AML patients undergoing alloHCT.
- Analyzed overall survival and relapse rates based on IDH1m status.
- Correlated IDH1m detection with co-mutations (NPM1, FLT3-ITD) and post-transplant outcomes.
Key Points:
- Pre-transplant CR1 IDH1m detection in 148 AML patients did not correlate with overall survival or relapse risk post-alloHCT.
- For AML patients with IDH1 mutations and co-existing NPM1/FLT3-ITD mutations, only persistent NPM1/FLT3-ITD predicted significantly higher relapse rates.
- This largest study to date suggests IDH1 mutation detection in CR1 blood is not a reliable indicator of AML MRD or increased post-transplant relapse risk.
Conclusions:
- IDH1 mutation status in pre-transplant CR1 blood is not a significant predictor of outcomes in adult AML patients undergoing alloHCT.
- NPM1 and FLT3-ITD mutations remain critical MRD markers in this setting.
- Further research may refine MRD detection methodologies for AML, but IDH1 mutations are not currently supported as independent prognostic markers for relapse risk.
