Impact of myelodysplasia-related and additional gene mutations in intensively treated patients with -mutated AML.

This study aimed to evaluate the impact of the myelodysplasia-related gene (MRG) as well as additional gene mutations on outcomes in intensively treated patients with -mutated ( ) AML. Targeted DNA sequencing of 263 genes was performed in 568 AML patients (median age: 59 years) entered into the prospective AMLSG 09-09 treatment trial. Most commonly co-mutated genes were (49.8%), -TKD (25.9%), (24.8%), (22.7%), (21.7%), (21.3%), (18%), and -ITD (17.3%). MRG mutations were identified in 18.1% of cases (18-60 years: 9.8%; >60 years: 28.7%). When focusing on the 470 patients with 2022 ELN favorable-risk AML, multivariable analysis for event-free survival (EFS) identified age ( < 0.001), ( < 0.001), ( = 0.007), and MRG mutations ( = 0.03) as unfavorable factors, cohesin gene co-mutations ( = 0.001) and treatment with gemtuzumab ozogamicin ( = 0.007) as favorable factors. Restricting the analysis to a subset of CR/CRi patients with available data on measurable residual disease (MRD) status in blood post cycle 2 in the model, MRG mutations lost their significant effect, whereas , , and cohesin gene mutations retained the adverse and favorable effects. For OS, age ( < 0.001), ( = 0.042), ( = 0.045), and (0.003) mutations were unfavorable factors, sole favorable factor was co-mutation ( = 0.037). In 2022 ELN favorable-risk AML, MRG mutations are associated with inferior EFS; however, this effect is no longer present when considering MRD status post cycle 2; and mutations remained adverse, and cohesin gene mutations favorable prognostic factors independent of the MRD status.