Abstract: The presence of FLT3-ITD mutation is associated with relapse and poor survival in AML patients. Venetoclax combined with hypomethylating agents (VEN+HMA) was approved for the frontline treatment of elderly or unfit AML patients, which leads to noteworthy impacts on AML management. The combination therapy is associated with encouraging efficacy in FLT3-mutated AML among both newly diagnosed unfit and relapsed/refractory patients. However, we found that two AML patients with FLT3-ITD mutation did not respond to venetoclax plus azacitidine (VEN+AZA). Given that the combined efficacy of venetoclax and the FLT3 inhibitor has been proved in pre-clinical models of FLT3+ AML, it is a scientific rationale to investigate venetoclax combined with the FLT3 inhibitor in AML patients with FLT3-ITD mutation. This is the first report of assessing the safety and response of gilteritinib (the first and only targeted second-generation FLT3 tyrosine kinase inhibitor approved by the US FDA) and venetoclax-based therapy in two AML patients with FLT3-ITD mutation unresponsive to VEN+AZA, which may bring new hope to FLT3 mutated patients who are unresponsive to VEN+HMA.
Keywords: acute myeloid leukaemia, FLT3-ITD, gilteritinib, venetoclax