Gene Mutation and MRD-Directed Risk Stratification Treatment Improves Long Term Survival of the Patients with AML1-ETO-Positive AML

Purpose: Aim to explore whether risk stratification treatment could improve the disease outcome of the patients with AML1-ETO-positive acute myeloid leukemia (AE-AML) based on gene mutation with next generation sequencing (NGS) and measurable residual disease (MRD) monitoring.

Method: A prospective cohort study (NCT02936089) about newly diagnosed AE-AML was performed in five medical centers in China from October 2016 to December 2021. Gene mutations were detected with NGS. MRD monitoring of RUNX1-RUNX1T1 transcript was assessed with quantitative polymerase chain reaction. After two cycles of consolidation, patients received risk stratification treatment as follow. Low risk (LR) group (C-KIT-ASXL1- with main molecular response (MMR)) was recommended to chemotherapy or autologous hematopoietic stem cell transplantation (auto-HSCT). Intermediate risk (IR) group (C-KIT+/ASXL1+ with MMR) was suggested for auto-HSCT or HLA-matched sibling HSCT. High risk (HR) group (C-KIT+ASXL1+ or without MMR) was treated with allogeneic (allo-) HSCT.

Result: Totally 198/207 patients including C-KIT-ASXL1- (n=100), C-KIT+/ASXL1+ (n=83) and C-KIT+ASXL1+ (n=15) were available for efficacy analysis in this study. Among the three groups, there was significantly different in the rate of 3-year overall survival (OS) (C-KIT-ASXL1-, 83.1% vs C-KIT+/ASXL1+, 67.4% vs C-KIT+ASXL1+, 23.0%，P<0.001) and cumulative incidence of relapse (CIR) (31.7% vs 33.9% vs 70.4%，P=0.001), while similar in the rate of CR and MRD negative after two cycles of induction (P>0.005). After two cycles of consolidation, the patients were stratified into LR (n=66), IR (n=57) and HR (n=72) groups.The 3-year OS rate (90.5% vs 71.4% vs 57.8%, P<0.001）and CIR (22.9% vs 31.9% vs 48.5%, P<0.001) were apparently different among the three groups. In the three risk groups, the patients following the treatment protocol all had significantly higher 3-year OS (LR 95.0% vs 86.1%，P=0.160; IR 92.3% vs 52.5%, P=0.006; HR 74.3% vs 25.0%, P<0.001) and lower CIR (LR 15.6% vs 27.2%，P=0.048; IR 15.0% vs 48.7%，P=0.006; HR 25.0% vs 84.1%，P<0.001) than those with bias treatment.

Conclusion: AE-AML could be further risk stratified based on C-KIT/ASXL1 mutation status and MRD levels after two cycles of consolidation. Gene mutation and MRD-directed risk stratification treatment would improve the long term survival of AE-AML patients.

No relevant conflicts of interest to declare.