Clinical Features of Flt3 Mutations in Acute Myeloid Leukemia Cases and the Role of Flt3 Inhibitors in the Treatment of Acute Myeloid Leukemia: A Single Center Experience

Abstract

AML is an aggressive and mortal disease. Worldwide, approximately 120.000 new AML cases and over 100.000 AML-related deaths occur each year and FLT3 mutations contribute to poor prognosis in AML. FLT3 mutations of 149 patients aged 20-95 years who were diagnosed with AML in our clinic were evaluated retrospectively. Relapse/refractory disease was found in 87.2% of these cases and FLT3 mutation in 25.5%. Of mutation-positive cases 65.8% had FLT3-ITD mutation and 34.2% had FLT3-TKD mutation. In our study, 38 patients with newly diagnosed FLT3 mutations were treated with FLT3 inhibitors such as midostaurin, sorafenib, and sunitinib in combination with chemotherapy and 76.3% (n:29) of the patients with FLT3 mutation received midostaurin. Mortality rate was higher in those with FLT3-TKD mutation compared to those with FLT3-ITD mutation. The risk of mortality in patients who received midostaurin and chemotherapy was 2.0 times higher than the control group, which consisted mostly of relapsed/refractory patients who received only chemotherapy. The cumulative mortality rate in all patients was 66.4%, with a median OS of 44.8 months. Increasing age (HR: 1.03; p<0.001), presence of FLT3 mutation (HR: 1.82; p=0.007), presence of relapse/refractory disease (HR: 23.66; p=0.002) were associated with higher mortality. Mortality risk was low in patients with allogeneic stem cell transplantation (HR: 0.19; p<0.001). When the survival rate was analyzed according to FLT3 mutation, the presence of FLT3 mutation negatively affected survival (HR: 1.82). In conclusion, our study is important as it has the highest number of patients in the efficacy analysis of FLT3 inhibitors in our region, as far as we know. The prognostic impact of FLT3-TKD mutations remains mysterious due to the low frequency. Further studies recruiting more patients may be useful to better understand the efficacy of FLT3 inhibitors in patients with FLT3-TKD mutations.