Rapid and Efficient Response to Gilteritinib and Venetoclax-Based Therapy in Two AML Patients with FLT3-ITD Mutation Unresponsive to Venetoclax Plus Azacitidine

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

Data Sharing Statement

The data sets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Ethics Approval and Informed Consent

The study was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University and was conducted in accordance with the Declaration of Helsinki. Both patients provided written informed consent, and they consented to the publication of their clinical details.

Disclosure

Lei-Si Zhang, Jun Wang, and Ming-Zhu Xu are co-first authors for this study. The authors declare that they have no conflicts of interest in this work.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China [Grant No. 81970138], Translational Research Grant of NCRCH [Grant No. 2020ZKMB05], Jiangsu Province “333” project, Social Development Project of the Science and Technology Department of Jiangsu (Grant No. BE2021649), Gusu Key Medical Talent Program [Grant No. GSWS2019007], and China Scholarship Council(No. 202106920030).