FLT3 targeting in the modern era: from clonal selection to combination therapies

Abstract

Fms-like tyrosine kinase 3 (FLT3) is the most frequently mutated gene in acute myeloid leukemia (AML). Modern targeting of FLT3 with inhibitors has improved clinical outcomes and FLT3 inhibitors have been incorporated into the treatment of AML in all phases of the disease, including the upfront, relapsed/refractory and maintenance settings. This review will discuss the current understanding of FLT3 biology, the clinical use of FLT3 inhibitors, resistance mechanisms and emerging combination treatment strategies.

Latest Insights and Progress in the Clinical Management of Elderly Patients with Acute Myeloid Leukemia: From Genetic Advancements to Targeted Treatments

“…In addition, patients with these mutations also tend to have shorter progression-free survival (PFS) and OS. In particular, FLT-3 ITD mutations significantly affect the complexity of disease biology and prognosis [53][54][55]. Other genetic abnormalities are potential targets for specific drugs [43,44,56,57].…”

“…Interestingly, in responsive patients fit for allogeneic SCT, CPX-351 is a feasible bridging measure [96]. Notably, low-intensity therapy, such as HMA/venetoclax [88][89][90][91]97,98] and molecularly tailored treatments [54,56,99], have been proven reliable bridges to allogeneic SCT. However, due to the frailty of older patients with comorbidities as well as socioenvironmental factors, the decision to undergo a transplant must be carefully considered by evaluating the treatment-related morbidity associated with allogenic SCT [1,4.88,92].…”