Measurable Residual IDH2 before Allogeneic Transplant for Acute Myeloid Leukemia

We recently reported that detection of residual NPM1 or FLT3-ITD variants in adult acute myeloid leukemia (AML) patients in first complete remission (CR1) prior to allogeneic hematopoetic cell transplant (alloHCT) is associated with increased relapse and death after transplant, but the prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark remains incompletely defined. Here we examined the clinical utility of residual IDH2 variants (IDH2m) in pre-transplant CR1 blood of 252 adult patients undergoing alloHCT for IDH2-mutated AML at a CIBMTR site between 2013-2019. NGS MRD analysis detected residual IDH2 variants in remission samples of 130 patients (51%) with variant allele fraction (VAF) ranging from 0.05-56% (median: 3%), and 100% validation by ddPCR. NGS MRD IDH2 positive patients had increased rates of relapse and decreased OS compared to those who tested negative. The impact of co-mutation status was examined by subdividing the cohort based on the presence of NPM1 or FLT3-ITD mutations at baseline. Residual IDH2 variants in patients without baseline NPM1 or FLT3-ITD co-mutations (n = 151) were associated with decreased OS and increased relapse . In contrast, residual IDH2 variants were not predictive of relapse in comutatedpatients.