Vanflyta (quizartinib)

In conclusion, the addition of Quizartinib to intensive chemotherapy, delayed until chemotherapy course 2, prolonged OS in older patients with FLT3-mutated AML but did not improve OS in non-FLT3 selected patients. ISRCTN-31682779, EudraCR-2013-002730-21.

Second-generation FLT3 inhibitors significantly improve survival outcomes in FLT3-mutated AML, particularly for gilteritinib and in relapsed/refractory disease. Further studies are needed to clarify mutation subtype-specific and dose-specific effects.

The risk-based approach and use of targeted therapies in CHIP-AML22 illustrate a shift toward more personalized treatment. Besides improving event-free survival, this study aims to contribute to the international consensus on strategies to reduce toxicity for all patients. The design of this study provides a dynamic framework, allowing for the potential introduction of emerging therapeutic options in the future.

Notably, the combination of 6k and the FLT3 inhibitor quizartinib showed significant synergistic antiproliferative effects both in vitro and in vivo. Mechanistic studies showed that this combined strategy could simultaneously inhibit glycolysis and OXPHOS by blocking the PI3K/AKT signaling pathway, ultimately exerting antitumor activity. In summary, this study highlights 6k as a potential metabolic regulator and provides a promising therapeutic strategy for AML.

These results suggest that concomitant use of quizartinib and moderate CYP3A inducers should be avoided. Concomitant use of weak CYP3A inducers does not warrant dose adjustment, since the impact on quizartinib exposure is clinically nonrelevant.

P1/2, N=52, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

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.

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.

In vivo, FYJ-195 induced profound tumor regression (TGI = 125%) in the MV4-11 xenograft model (10 mg/kg) and achieved robust tumor growth suppression (TGI = 68.6%) in the Ba/F3-FLT3-ITD-F691L model (50 mg/kg), where quizartinib was ineffective. Mechanistic studies confirmed that FYJ-195 effectively blocked FLT3 signaling and induced apoptosis without observable toxicity. Collectively, FYJ-195 represents a promising lead candidate for drug-resistant AML.

In patients with newly diagnosed FLT3-ITD-negative AML achieving CRc1, quizartinib improved OS and DFS in the overall population. Notably, the clinical benefit of quizartinib was observed regardless of allo-HCT, and appeared more evident in patients who did not proceed to transplant.

P1/2, N=113, Completed, PETHEMA Foundation | Recruiting --> Completed | N=84 --> 113 | Trial completion date: Nov 2024 --> May 2025

These subnetworks included hub genes such as IFIT1, PSMB9, and HLA-B, which are known to be associated with immune evasion and drug resistance in acute myeloid leukemia. Our findings demonstrate that the proposed method enables statistically reliable and biologically interpretable identification of phenotype-specific gene regulatory mechanisms, providing insights into potential therapeutic targets.