A phase I/II study of gilteritinib in combination with chemotherapy in newly diagnosed patients with AML in Asia: final analysis

Background: Mutations in the FMS -like tyrosine kinase 3 ( FLT3 ) gene are present in approximately 30% of patients with newly diagnosed (ND) acute myeloid leukemia (AML), and are associated with worse therapy outcomes compared to the general AML population. Gilteritinib, a selective oral FLT3 inhibitor, is a promising treatment option for this patient population. Objectives: To assess the safety and efficacy of gilteritinib in combination with induction and consolidation chemotherapy in Asian patients with ND, FLT3 -mutated ( FLT3 mut+ ) AML. Design: This study was a phase I/II open-label, single-arm study. Herein, we present the final results from phase II. Methods: A total of 84 patients were enrolled in 33 centers across Japan, Korea, and Taiwan. All patients enrolled in phase II received induction and consolidation therapy with gilteritinib 120 mg/day plus chemotherapy (induction: ⩽2 cycles, idarubicin/cytarabine once-daily; consolidation: ⩽4 cycles, cytarabine twice-daily) followed by maintenance with gilteritinib 120 mg/day monotherapy (⩽26 cycles). The primary efficacy endpoint was the complete remission (CR) rate after induction therapy. Results: The primary endpoint of CR rate after induction was 50.0% (90% CI: 40.4–59.6). Gilteritinib in combination with chemotherapy achieved high composite CR (CRc; 86.6%, 95% CI: 77.3–93.1) rates after induction. The overall survival (OS) rate at 3 years was 71.6%, and the median OS was 48.2 months; however, due to the immaturity of the data, the median OS should be interpreted with caution. In addition, 51.2% of patients underwent hematopoietic stem cell transplantation during the study period. The safety profile of gilteritinib was as expected, and no new safety signals were identified. Conclusion: Induction and consolidation with gilteritinib plus chemotherapy, and maintenance with gilteritinib monotherapy were well tolerated in ND patients in Asia with FLT3 mut+ AML and had favorable efficacy compared with historical data. Trial registration: This trial was registered with the ClinicalTrials.gov identifier NCT02310321.