FLT3 mutation

P1, N=38, Recruiting, National Cancer Institute (NCI) | N=28 --> 38

In this large multicenter cohort, KIT and FLT3-ITD mutations did not adversely affect the prognosis of pediatric CBF-AML treated according to the C-HUANAN-AML-15 protocol. MRD after induction was the most powerful predictor of relapse and survival, underscoring its importance for risk stratification in future pediatric AML trials.

P1/2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P2, N=20, Recruiting, University of Florida | Trial completion date: May 2027 --> May 2028 | Trial primary completion date: May 2026 --> May 2027

Its mutation subtype, molecular context, treatment setting, assay performance and standardized reporting determine its diagnostic, prognostic, predictive and MRD-related value. This review offers a clinical laboratory perspective on how to interpret FLT3 mutations as actionable biomarkers in AML.

Moreover, FTY720 co-treatment resensitized G12D NRAS-mutated M14(R)701 cells to gilteritinib in vivo. Co-treatment inactivated ERK, transcriptionally downregulated SPHK1, and inactivated downstream AKT, p70 S6K and BAD, with inactivation abrogated by constitutive SPHK1 expression. The clinically applicable S1PR modulators fingolimod and mocravimod resensitize NRAS-mutated FLT3-ITD AML cells to FLT3 inhibitors, supporting potential clinical efficacy.

Gilteritinib was generally well-tolerated, with no observed increase in cytomegalovirus (CMV)-related or graft-versus-host complications. This study provides real-world evidence in a clinically relevant scenario and supports the use of gilteritinib maintenance in patients with FLT3-mutated AML who undergo transplantation during R/R disease.

From 2017 to 2024, FLT3 testing and guideline-concordant treatment were commonly implemented within this community health system, as demonstrated by real-world data derived from the electronic medical record (EMR). The findings highlight strengths in baseline molecular testing and treatment selection, while also identifying opportunities to improve, including in community-based settings. Opportunities remain to improve documentation practices, transitions of care, and molecular retesting at relapse. These findings support targeted quality improvement efforts to optimize molecular testing workflows and treatment alignment in AML.

Among the screened compounds, apigenin, chrysin, and sakuranetin showed the highest binding affinities toward FLT3, with docking scores of - 10.1, - 9.8, and - 9.9 kcal/mol, respectively, compared with - 8.7 kcal/mol for Quizartinib...ELF and molecular electrostatic potential (MEP) analyses were performed to characterize charge distribution and interaction regions. All computational tools and parameters are described in the main manuscript.

We performed multiomic single cell (SC) DNA/protein and RNA/protein profiling of a clinical trial cohort of acute myeloid leukemia (AML) patients treated on the Phase 1b clinical trial of the BCL2 inhibitor venetoclax and the FLT3 inhibitor gilteritinib (Ven/Gilt) to characterize immunophenotypic, transcriptional, and genetic clonal evolution driving resistance. These results underscore that RAS signaling is central to FLT3 and BCL2 inhibitor resistance, is tightly coupled to AML monocytic differentiation and highlight RAS pathway inhibition as a viable clinical strategy to combat resistance. CT# NCT03625505.

Here we detail two patient cases illustrating the real-world use of quizartinib in combination with anthracycline and cytarabine-based chemotherapy and maintenance monotherapy for the management of FLT3-ITD+ AML. These cases highlight the practical recommendations on management of quizartinib-based chemotherapy in accordance with the Food and Drug Administration (FDA)-mandated REMS requirements. Adopting these strategies to optimize the safe treatment of FLT3-ITD+ AML with quizartinib may ultimately improve patient outcomes in this highly challenging malignancy.

Randomized studies comparing this regimen to standard of care approaches are warranted. This trial is registered at www.clinicaltrials.gov #NCT04140487.