Journal: Haematologica
This retrospective study evaluated 73 patients with newly diagnosed FLT3-mutated AML treated with frontline triplet regimens combining a hypomethylating agent, venetoclax, and a FLT3 inhibitor.
The composite complete remission rate (CR + CRi) was 93%, with deep molecular responses achieved in a majority by cycle 4.
At 3 years:
- Relapse-free survival was 38% for FLT3-ITD and 76% for FLT3-TKD mutations.
- Overall survival was 45% and 76%, respectively.
Traditional prognostic factors and allogeneic stem cell transplant did not significantly affect survival.
However, baseline RAS pathway mutations were linked to poorer outcomes: 3-year overall survival was 22% vs. 63% without these mutations.
Most relapses involved FLT3 wild type clones, and new RAS mutations emerged in nearly a quarter of relapses.
Post-relapse survival was poor, especially with persistent FLT3 mutations.
Overall, these triplet regimens yield high remission rates and encouraging long-term survival in older adults with FLT3-mutated AML, though strategies to address FLT3 wild type relapse and RAS-mediated resistance remain necessary.