Efficacy and toxicity of FLT3 inhibitors in the treatment of acute myeloid leukemia in a clinical trial context - Systematic review

Abstract

Background: Acute myeloid leukemia (AML) is characterized by clonal proliferation of myeloblasts, with particular cytogenetic and molecular alterations. The FLT3 gene is mutated in approximately one-third of patients, confering a worse prognosis if there is internal tandem duplication. Several FLT3 inhibitors have been developed, with different specificities, pharmacokinetics and toxicities. Objective: Analyze the use of FLT3 inhibitors in the treatment of AML in different clinical scenarios and to clarify their efficacy and toxicity.Methodology: Systematic review of clinical trials with FLT3 inhibitors on the Web of Science and Pubmed, published between 2011 and 2021. Results: A total of 23 articles were included in this review, comprising phase II and III clinical trials evaluating seven FLT3 inhibitors (midostaurin, gilteritinib, sunitinib, sorafenib, quizartinib, lestaurtinib and pexidartinib). Experimental groups showed higher overall response rates in different clinical settings, an increased overall survival and a higher frequency of thrombocytopenia, neutropenia, anemia, febrile neutropenia and infections compared to control groups.Conclusion: FLT3 inhibitors led to improvements in the prognosis of patients with AML, either in the treatment of newly diagnosed cases or in cases of relapse/refractority, with an acceptable toxicity profile.