Measurable Residual IDH1 before Allogeneic Transplant for Acute Myeloid Leukemia.

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 ( IDH1 m) 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 IDH1 m 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.
Competing Interests: Conflicts of Interest Statements Hourigan: The National Heart, Lung, and Blood Institute receives research funding for the laboratory of Dr. Hourigan from the Foundation of the NIH AML MRD Biomarkers Consortium. Auletta: Advisory Committee: AscellaHealth and Takeda El Chaer: Consultant: SPD Oncology, Amgen, Association of Community Cancer Centers; Clinical Trial Grant Support (PI) to the University of Virginia: Amgen, BMS, Celgene, SPD Oncology, Sanofi, Bristol Myers Squibb, FibroGen, PharmaEssentia, BioSight, MEI Pharma, Novartis, Arog pharmaceuticals; Travel grant: DAVA Oncology E Chen: Consultant: Rigel Pharmaceuticals and AbbVie Corner: Employment: Bio-Rad Laboratories Jimenez Jimenez: Funding: Abbvie De Lima: Advisory Board: Pfizer, Bristol Myers Squibb; Data Safety Monitoring Board: Novartis, Abbvie; Research Funding: Miltenyi Biotec Kebriaei: Consultant: Pfizer, Jazz Pharmaceuticals