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Gene mutations linked to improved survival for high-dose chemotherapy in AML patients
Specific gene mutations were associated with improved OS for acute myeloid leukemia patients who underwent high-dose chemotherapy, according to study results.
A previous multisite study determined a more intense initial regimen using higher doses of daunorubicin significantly improved remission rate and improved OS. In the current study, researchers from the University Hospitals Case Medical Center performed an analysis of identified gene mutations that could have prognostic significance for AML patients.
The analysis examined 18 possible prognostic genes — including TET2, ASXL1, IDH1, IDH2, DNMT3A and PHF6 — in 398 patients aged younger than 60 years with AML. The patients were randomly assigned to receive either high-dose or standard-dose daunorubicin. An independent set of 104 patients was used to validate prognostic findings.
Researchers identified at least one somatic alteration in 97.3% of the patients. Researchers observed that several of these genetic mutations were associated with reduced OS, including internal tandem duplication in FLT3 (P=.001), partial tandem duplication in MLL (P=.009), and mutations in ASXL1 (P=.005) and PHF6 (P=.006).
Researchers also identified genetic predictors of outcome that improved risk stratification among patients with AML, independently of age, induction dose, white cell count and post-remission therapy. High-dose daunorubicin, as compared with standard dose daunorubicin, improved the rate of survival among patients with DNMT3A or NPM1 mutations or MLL translocations (P=.001), but not among patients with wild-type DNMT3A, NPM1 and MLL (P=.67).
“The data in this study show a way in which integrated mutational profiling of a clinical trial cohort can advance our understanding of the biologic characteristics of AML, improve current prognostic models and inform therapeutic decisions,” the researchers said. “Most important, these data indicate that more detailed genetic analysis may lead to improved risk stratification and identification of patients who can benefit from more intensive induction chemotherapy.”
Disclosure: The researchers report no relevant financial disclosures.