Measurable Residual IDH1 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 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. 53 patients (36%) tested positive for IDH1m persistence in CR1, with no difference between the IDH1m positive and negative groups (OS: p = 0.4; relapse: p = 0.5). For those patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). The remaining cohort did not show any significant outcome differences based on IDH1 persistence. These data, from the largest study to date, do not support the detection of isolated IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML measurable residual disease or increased post-transplant relapse risk.