Midostaurin added to standard therapy in FLT3-positive acute myeloid leukaemia treatment

Abstract

Acute myeloid leukaemia (AML) is a complex disease with a dynamic course associated with a series of acquired and cumulative genetic changes. In recent years, significant advances have been made in the understanding of its pathogenesis. Moreover, diagnostic and therapeutic options have expanded. The current classifications consider cytogenetic and molecular disorders, including the presence of, among others, mutations within FMS-like tyrosine kinase 3 (FLT3) transmembrane tyrosine kinase, regulating the proliferation and differentiation of hematopoietic cells at an early development stage. FLT3 mutation is detected in approximately 30% of newly diagnosed AML cases and concerns mutations: internal tandem duplication (ITD) or tyrosine kinase domain (TKD) gene. The high ratio of FLT3-ITD mutation is associated with an unfavourable prognosis. It is recommended to includ patients in clinical trials due to insufficient standard therapy effects. The new AML treatment strategies include first-and second-generation tyrosine kinase inhibitors. Midostaurin, a non-specific kinase inhibitor, was approved in 2017 for treatment of patients with newly diagnosed FLT3-positive AML in combination with standard chemotherapy. The paper presents the experience of the Department of Haematology and Bone Marrow Transplantation in Poznan in the use of FLT3 tyrosine kinase inhibitors based on a case report of two patients with newly diagnosed AML.