Quizartinib for FLT3-ITD AML: Induction-Consolidation-Maintenance and QT Monitoring

　　1.Eligibility Boundary

　　Quizartinib is an oral type II FLT3 kinase inhibitor for:

　　adults;

　　newly diagnosed AML;

　　FLT3-ITD positive by authorized testing;

　　combination with chemotherapy and post-consolidation maintenance.

　　Key limits:

　　FLT3-ITD only,not generic“FLT3 mutation positive”;

　　FLT3-TKD point mutation not in indication;

　　relapsed/refractory AML not covered by this newly diagnosed label;

　　single-agent maintenance after allogeneic HSCT not indicated.

　　2.Mechanism

　　FLT3-ITD causes constitutive activation and drives leukemic proliferation.Quizartinib selectively inhibits FLT3 kinase activity,blocking downstream survival signaling and improving clearance of FLT3-ITD clones during chemotherapy.

　　It is not chemotherapy replacement and not a standalone universal AML drug.

　　3.Standard Pathway

　　Induction

　　With cytarabine+anthracycline(7+3):

　　up to 2 cycles;

　　quizartinib from day 8;

　　aim for complete remission.

　　Consolidation

　　With high-dose cytarabine:

　　up to 4 cycles;

　　continue FLT3 coverage;

　　if allo-HSCT planned,stop quizartinib 7 days before conditioning.

　　Maintenance

　　After count recovery(ANC>500/µL,platelets>50,000/µL):

　　26.5mg once daily start;

　　escalate to 53mg day 15 if QTcF≤450ms;

　　up to 36 cycles;

　　stop on progression or unacceptable toxicity.

　　4.Who Should Not Use This Pathway

　　Not appropriate for:

　　FLT3-ITD negative;

　　FLT3-TKD only;

　　R/R AML outside newly diagnosed label;

　　post-allo-HSCT single-agent maintenance:label excludes it,OS benefit not shown;

　　long QT syndrome,severe hypokalemia/hypomagnesemia;

　　QTcF>450ms at initiation or escalation.

　　5.QT and Cardiac Safety

　　Boxed warning:QT prolongation,torsades de pointes,cardiac arrest.

　　Monitoring:

　　baseline ECG;

　　weekly ECG during induction/consolidation;

　　weekly first month of maintenance then clinically;

　　correct potassium/magnesium;

　　avoid stacking QT-prolonging drugs;

　　do not start/escalate if QTcF>450ms;hold if>500ms.

　　Strong CYP3A inhibitors raise quizartinib exposure;reduce dose.

　　6.Other Safety

　　cytopenias,febrile neutropenia;

　　infection prophylaxis as needed;

　　severe hepatic impairment not studied;

　　pregnancy testing,contraception in reproductive-potential patients;

　　miss dose same day,no double dose;

　　prescribed by AML hematology team under REMS-style controls.