Photo Credit: Md Babul Hosen

The following is a summary of “Only FLT3-ITD co-mutation did not have a deleterious effect on acute myeloid leukemia patients with NPM1 mutation, but concomitant with DNMT3A co-mutation or a < 3log reduction of MRD2 predicted poor survival,” published in the September 2024 issue of Hematology by Duan et al.

Researchers conducted a retrospective study assessing how gene co-mutations and NPM1 measurable residual disease (MRD) affect outcomes in patients with acute myeloid leukemia (AML), mainly focusing on those with the rare type of NPM1 mutation (MPN1^RT).

They analyzed 234 patients with AML, with 11.5% carrying the NPM1RT mutation. The median age of participants was 49 years (IQR: 36-58), and the median follow-up period was 30.4 months (IQR: 12.1-55.7). Researchers focused on mutations in 9 genes that appeared in more than 10% of patients, with DNMT3A (53.8%) and FLT3-ITD  (44.4%) being the most common. Univariable analysis was performed on 137 individuals to assess how FLT3-ITD, DNMT3A co-mutations, and MRD2 <3 log reduction affected survival rates. The multivariable analysis further identified key independent survival predictors. 

The results showed that in the univariable analysis, patients with FLT3-ITD and DNMT3A co-mutations and those with an MRD2 < 3 log reduction demonstrated poorer survival outcomes. Individuals with both FLT3-ITD and DNMT3A co-mutations experienced the lowest 3-year event-free survival (30.0%) and overall survival (OS, 34.4%, both P<0.001). Findings revealed that FLT3-ITD alone did not worsen outcomes. Multivariable analysis confirmed DNMT3A co-mutation (EFS: HR=1.9, P=0.021, OS: HR=2.2, P=0.023) and MRD2 ≥ 3 log reduction (EFS: HR=0.2; OS: HR=0.1; both P<0.001) as independent survival predictors. Allo-HSCT improved survival significantly compared to chemotherapy alone (3-year EFS: 57.9% vs. 30.0%, P-0.012, OS: 72.9% vs. 34.4%, P=0.001). 

Investigators concluded that patients with AML and NPM1 mutations have worse survival when both FLT3-ITD and DNMT3A co-mutations are present. Based on these mutations or MRD2 < 3 log reduction, high-risk individuals benefit more from allo-HSCT than chemotherapy.

Source: link.springer.com/article/10.1007/s00277-024-06001-6