Sorafenib plus intensive chemotherapy improves survival in patients with newly diagnosed, FLT3-internal tandem duplication mutation–positive acute myeloid leukemia

Background: The addition of midostaurin to induction chemotherapy improves survival in younger patients with newly diagnosed, FLT3–mutated acute myeloid leukemia (AML). Sorafenib is a potent multikinase inhibitor with efficacy when given as monotherapy. The authors investigated whether the addition of sorafenib to intensive induction chemotherapy improves outcomes in patients with FLT3-internal tandem duplication (ITD)–mutated AML. Methods: In total, 183 patients who were newly diagnosed with FLT3-ITD–mutated AML between February 2001 and December 2017 were identified. Of these, 79 patients (43%) underwent intensive chemotherapy with the addition of sorafenib, and 104 (57%) received intensive chemotherapy alone. Propensity score matching identified 42 patients in each cohort. Results: The overall response rate was 98% in the sorafenib cohort and 83% in the intensive chemotherapy cohort (P =.057). The median follow-up was 54 months. The median event-free survival was 35 months in the sorafenib cohort and 8 months in the intensive chemotherapy cohort (P =.019), and the median overall survival was 42 and 13 months, respectively (P =.026). With censoring at the time of allogeneic stem cell transplantation, the median event-free survival was 31 and 8 months in the sorafenib and intensive therapy cohorts, respectively (P =.031), and the median overall survival was not reached and 10 months, respectively (P =.001). Multivariate Cox proportional hazards models confirmed that treatment with sorafenib was a favorable prognostic factor (P =.009; hazard ratio, 0.558; 95% CI, 0.360-0.865). Conclusions: The addition of sorafenib improves survival in patients with FLT3-ITD–mutated AML regardless of whether they undergo allogeneic stem cell transplantation.