[Pharmacological and clinical profile of gilteritinib (Xospata tablets 40 mg), a therapeutic agent for relapsed or refractory FLT3-mutated acute myeloid leukemia].

Gilteritinib fumarate (Xospata tablets 40 mg) is a novel, highly selective, oral FMS-like tyrosine kinase 3 (FLT3) inhibitor used for the treatment of patients with relapsed or refractory FLT3-mutated acute myeloid leukemia (AML), and it was approved in Japan in September 2018. Preclinical studies demonstrated that gilteritinib inhibited FLT3 and showed antiproliferative activity against Ba/F3 cells expressing mutated FLT3. In addition, gilteritinib inhibited tumor growth, induced tumor regression, and prolonged survival in mice xenografted with MV4-11 cells endogenously expressing FLT3-internal tandem duplication. In clinical trials conducted in the United States, Europe, and Japan, plasma concentrations after administration of gilteritinib 20 to 450 mg/day were generally dose proportional, and gilteritinib was well tolerated. Multiple clinical trials, including a global Phase III study, in patients with relapsed or refractory FLT3-mutated AML treated with gilteritinib demonstrated higher response rates of complete remission or complete remission with partial hematologic recovery and longer overall survival compared with patients treated with salvage chemotherapy. Some clinical trials are ongoing in patients with FLT3-mutated AML at various treatment stages, such as induction therapy, maintenance therapy, and treatment after hematopoietic stem cell transplantation. In conclusion, in vitro, in vivo, and clinical data indicate that gilteritinib fumarate is an effective treatment option in adult patients with relapsed or refractory FLT3-mutated AML in Japan.