FLT3 positive

Gilteritinib exhibited promising outcomes by targeting FLT3 receptors, offering a new treatment approach, and revealing improved overall survival compared to salvage chemotherapy in the difficult-to-treat patient population.

The complete remission (P = 0.48) and the overall survival rates were similar (P >0.05). Except for an increased rate of acute leukaemia and a lower platelet count, the COVID-19 pandemic did not impact the presentation and outcomes of acute leukaemia.

Our results suggest different immunosuppressive effects of these three FLT3i and may, therefore, provide an additional rationale for optimal maintenance therapy after alloHSCT of FLT3-positive AML patients to prevent infectious complications and GvHD mediated by DCs.

P1/2, N=74, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

In validation, MPhos outperformed the currently-used FLT3-based stratification method. Our findings have the potential to transform clinical decision-making, and highlight the important role that phosphoproteomics is destined to play in precision oncology.

P1/2, N=74, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Study findings showed that there was a lack of routine testing for FLT3 mutations at first diagnosis of R/R AML, and initial treatment decisions did not differ by FLT3 mutation status. Given the clinical burden of FLT3MUT, likelihood of FLT3 status changes, and emerging FLT3 inhibitors, further routine FLT3 screening is needed to optimize treatment of R/R AML.

P2, N=22, Completed, Randy Windreich | Active, not recruiting --> Completed | Trial completion date: Nov 2023 --> Apr 2023 | Trial primary completion date: Nov 2023 --> Apr 2023

P1/2, N=74, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Dec 2023 --> Dec 2024

Novel drug combinations and strategies against FLT3 mutated AML are currently under investigation and will be the focus of future studies. The development of more selective and potent FLT3 inhibitors may further improve outcomes for patients with FLT3-positive AML. Monitoring minimal residual disease and overcoming resistance are key issues for the future.

This phase 1 study has demonstrated an acceptable safety profile and a significant anti-leukaemic activity of clifutinib in FLT3 mutant R/R AML, with the best response at the dose of 40 mg/day in FLT3-ITD(+)/TKD(-) AML. A confirmatory phase 3 study is currently ongoing to further evaluate the efficacy and safety of clifutinib dosed at 40 mg/day in R/R AML pts after first-line therapy with FLT3-ITD(+)/TKD(-) (NCT05586074).