RESUMO
BACKGROUND: Acute myeloid leukemia (AML) is a complex disease with diverse mutations, including prevalent mutations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene that lead to poor prognosis. Recent advancements have introduced FLT3 inhibitors that have improved outcomes for FLT3-mutated AML patients, however, questions remain on their application in complex conditions such as relapsed/refractory (R/R) disease. Therefore, we aimed to evaluate the clinical effectiveness of second-generation FLT3 inhibitors in treating patients with R/R AML. METHODS: A systematic literature search of PubMed, MEDLINE, SCOPUS and Google Scholar databases was made to identify relevant studies up to January 30, 2024. This study was conducted following the guidelines of the PRISMA. RESULTS: The ADMIRAL trial revealed significantly improved overall survival and complete remission rates with gilteritinib compared to salvage chemotherapy, with manageable adverse effects. Ongoing research explores its potential in combination therapies, showing synergistic effects with venetoclax and promising outcomes in various clinical trials. The QuANTUM-R trial suggested longer overall survival with quizartinib compared to standard chemotherapy, although concerns were raised regarding trial design and cardiotoxicity. Ongoing research explores combination therapies involving quizartinib, such as doublet or triplet regimens with venetoclax, showing promising outcomes in FLT3-mutated AML patients. CONCLUSION: These targeted therapies offer promise for managing this subgroup of AML patients, but further research is needed to optimize their use. This study underscores the importance of personalized treatment based on genetic mutations in AML, paving the way for more effective and tailored approaches to combat the disease.
Assuntos
Leucemia Mieloide Aguda , Inibidores de Proteínas Quinases , Tirosina Quinase 3 Semelhante a fms , Humanos , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Tirosina Quinase 3 Semelhante a fms/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Inibidores de Proteínas Quinases/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Mutação , Compostos de Anilina/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Pirazinas/uso terapêutico , BenzotiazóisRESUMO
The evaluation of diagnostic and prognostic biomarkers has always been a hot topic in various diseases. Considering that cardiovascular diseases (CVDs) have the highest mortality and morbidity rates in the world, various studies have been conducted so far to find CVD associated biomarkers, including cardiac troponin (cTn) and NT-proBNP. Cytokines are components of the immune system that are involved in the pathogenesis of CVD due to their contribution to the inflammation process. The level of cytokines varies in many cardiovascular diseases. For instance, the plasma level of IL-1α, IL-18, IL-33, IL-6 and IL-8 is positively correlated with atherosclerosis and that of some other interleukins such as IL-35 is negatively correlated with acute myocardial infarction or cardiac angina. Due to its pivotal role in the inflammation process, IL-1 super family is involved in many CVDs, including atherosclerosis. IL-20 among the interleukins of IL-10 family has a pro-atherogenic role, while others, such as IL-10 and IL-19, play an anti-atherogenic role. In the present review, we have collected the latest published evidence in this respect to discuss valuable cytokines from the diagnostic and prognostic stand point in CVDs.