Outcomes of patients with newly diagnosed acute myeloid leukemia with FLT3-tyrosine kinase domain mutations: Prognostic implications of NPM1 co-mutation.
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BACKGROUND: The prognostic impact of Fms-like tyrosine kinase 3 (FLT3)-tyrosine kinase domain (TKD) mutation in patients with acute myeloid leukemia (AML) is not well defined. The authors described outcomes of one of the largest cohorts of patients with FLT3-TKD mutated (FLT3-TKDmut) AML to date. METHODS: This retrospective study included patients with newly diagnosed AML who received frontline treatment at The University of Texas MD Anderson Cancer Center from January 2012 to March 2024 divided into two cohorts: FLT3-TKDmut AML and nucleophosmin-mutated (NPM1mut)/FLT3-TKD wild-type (FLT3-TKDwt) AML. Patients with FLT3 internal tandem duplication mutations were excluded. RESULTS: In total, 2922 patients were screened, and 250 met inclusion criteria, including 124 patients with FLT3-TKDmut AML and 126 patients with NPM1mut/FLT3-TKDwt AML. In the FLT3-TKDmut cohort (n = 124), intensive chemotherapy was received by 54 patients (44%), with a composite complete remission in 81% and a 3-year overall survival (OS) rate of 56%. An NPM1 mutation was noted in 24 patients (44%) who had improved OS (3-year OS, 74% vs. 40%; p = .03). Allogeneic stem cell transplantation improved OS in patients who had NPM1wt AML (3-year OS, 89% vs. 30%; p = .02) but not in those who had an NPM1 mutation. Lower intensity therapy was received by 70 patients (56%), with a composite complete remission in 63% and a 3-year OS rate of 23%. An NPM1 mutation was noted in 31 patients (44%) who had improved OS (3-year OS, 32% vs. 16%; p = .04). Allogeneic stem cell transplantation led to a trend toward improved OS in patients who had NPM1wt AML (3-year OS, 75% vs. 27%; p = .1) but not in those who had NPM1mut AML. In the NPM1mut/FLT3-TKDwt cohort (n = 126), intensive chemotherapy was received by 46 patients (37%), and lower intensity therapy was received by 80 patients (63%). Compared with the NPM1mut/FLT3-TKDmut cohort, no difference in OS was noted between patients who received intensive chemotherapy and those who received lower intensity therapy. CONCLUSIONS: FLT3-TKDmut AML commonly harbors NPM1 co-mutation, which has key prognostic implications. Lack of NPM1 co-mutation portends a poor prognosis, and allogenic stem cell transplantation should be strongly considered for patients in first remission.