OncoTargets and Therapy (Feb 2022)
Rapid and Efficient Response to Gilteritinib and Venetoclax-Based Therapy in Two AML Patients with FLT3-ITD Mutation Unresponsive to Venetoclax Plus Azacitidine
Abstract
Lei-Si Zhang,1,2,* Jun Wang,1,2,* Ming-Zhu Xu,1,2,* Tian-Mei Wu,1,2 Si-Man Huang,1,2 Han-Yu Cao,1,2 Ai-Ning Sun,1,2 Song-Bai Liu,3 Sheng-Li Xue1,2 1National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of China; 3Suzhou Key Laboratory of Medical Biotechnology, Suzhou Vocational Health College, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Song-Bai Liu, Suzhou Key Laboratory of Medical Biotechnology, Suzhou Vocational Health College, No. 28, Kehua Road, Suzhou, 215009, People’s Republic of China, Tel +86-13862145806, Email [email protected] Sheng-Li Xue, National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, 215006, People’s Republic of China, Tel +86-512-67781856, Email [email protected]: 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
