Prognostic significance of baseline FLT3-ITD mutant allele level in acute myeloid leukemia treated with intensive chemotherapy with/without sorafenib

Abstract

Internal tandem duplication (ITD) of the fms-related tyrosine kinase-3 gene (FLT3) confer a poor prognosis in adult AML. Studies have reported that a higher mutant allelic burden is associated with a worse prognosis. Adult patients with FLT3-ITD mutated AML treated at our institution were identified. Patients were assigned into 2 groups; patients who received idarubicin and cytarabine (IA, group one) containing induction, and who received sorafenib in addition to IA containing regimens at induction (group two). The optimal FLT3-ITD mutant allele cut-off was defined as the cut-off to divide the whole cohort with the highest statistical significance. A total of 183 patients including 104 (57%) in group one and 79 (43%) in group two were identified. The complete remission (CR)/CR with incomplete hematologic recovery (CRi) for group one and group two were 85% and 99%, respectively (P = .004). The median relapse free survival (RFS) for group one and two were 12 and 45 months, respectively (P = .02). The median overall survival (mOS) was 17 months in group one, and has not been reached in group two (P = .008). The optimal FLT3-ITD mutant allele cut-off for OS was 6.9% in group one, there was no optimal cut-off in group two. On multivariate analysis, poor performance status (PS) (P = .003), sorafenib (P = .01), and presenting white blood cells (WBC) (P < .001) were independent predictors of OS. Higher FLT3-ITD allele burden is associated with a worse outcome in patients treated with IA-based chemotherapy. Addition of sorafenib to chemotherapy not only nullifies the negative prognostic impact of higher allele burden, but also improves outcome of FLT3-ITD mutated AML patients regardless of the allele burden.