QUIZARTINIB TAB
Clinical Criteria Summary
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Indication & Population
- Adults with newly diagnosed acute myeloid leukemia (AML) that is FLT3-ITD–positive as detected by an FDA-approved test
- Used in combination with standard cytarabine and anthracycline induction, cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy
- Not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (alloHCT) due to lack of demonstrated overall survival improvement
Dosing & Administration
- Induction (7 + 3 regimen): 35.4 mg PO once daily on Days 8–21 of a 28-day cycle (Days 6–19 for 5 + 2 regimen)
- Consolidation: 35.4 mg PO once daily on Days 6–19 for up to 4 cycles
- Maintenance: 26.5 mg PO once daily on Days 1–14 of first cycle if QTcF ≤ 450 ms; increase to 53 mg once daily on Day 15 if QTcF ≤ 450 ms; maintain 26.5 mg once daily if QTcF > 500 ms during induction or consolidation
- Continue maintenance regimen without breaks between cycles for up to 36 cycles
- Available as 17.7 mg and 26.5 mg tablets
Contraindications
- Severe hypokalemia (< 3 mmol/L)
- Severe hypomagnesemia (grade 3 < 0.4 mmol/L)
- Long QT syndrome (LQTS)
- History of ventricular arrhythmias or torsade de pointes
Monitoring & Safety Requirements
- Monitor for and correct hypokalemia and hypomagnesemia
- Perform ECGs at baseline, weekly during induction and consolidation therapy, weekly for at least the first month of maintenance, and periodically thereafter
- Available exclusively through the VANFLYTA REMS restricted distribution program due to serious risks of QT prolongation, torsade de pointes, and cardiac arrest
Drug Interactions
- Strong CYP3A inhibitors: Reduce quizartinib dosage
- Strong or moderate CYP3A inducers: Avoid co-use
- QT interval prolonging drugs: Monitor patients more frequently with ECG
Special Populations
- Pregnancy: Can cause embryofetal harm; advise patients who can become pregnant of potential risk to a fetus
- Lactation: Avoid breastfeeding during treatment and for one month after the last dose
VA Formulary Criteria
- Indicated for newly diagnosed FLT3-ITD–positive AML patients with an absolute contraindication to midostaurin, used in combination with standard chemotherapy for induction/consolidation and as maintenance monotherapy following consolidation without alloHCT
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Diagnosis & Clinical Indication
- Newly diagnosed acute myeloid leukemia (AML) positive for FLT3 internal tandem duplication (ITD) mutation
- Has an absolute contraindication or unmanageable intolerance to midostaurin
Treatment Regimen & Dosing Considerations
- Use in combination with standard cytarabine and anthracycline induction and cytarabine consolidation regimens
- Use as maintenance monotherapy following consolidation chemotherapy
- When used concomitantly with strong CYP3A inhibitors: Dose of quizartinib is reduced as per prescribing information
Patient Selection & Performance Status
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Goals of care and role of Palliative Care consult have been discussed and documented
Safety, Monitoring & Exclusion Criteria
- Uncorrected severe hypokalemia (< 3 mmol/L) or severe hypomagnesemia (< 0.4 mmol/L)
- History of ventricular arrhythmias or torsade de pointes
- Prolonged QTc interval (at baseline or during monitoring as recommended in prescribing information), including history of long QT syndrome
- Use for maintenance monotherapy following allogeneic hematopoietic stem cell transplantation
- Concomitant strong or moderate CYP3A inducers and unmanageable drug-drug interactions
- Inability to swallow the tablets whole
Special Populations & Counseling Requirements
- Pregnant patients: Advised of the potential risk to a fetus
- Patients who can become pregnant: Pregnancy status verified within 7 days pre-treatment; counseled on potential risks vs benefits and use of effective contraception during treatment and for up to 7 months after the last dose
- Males with female partners who can become pregnant: Counseled on potential risks vs benefits and use of effective contraception during treatment and for up to 4 months after the last dose
- Lactating patients: Advised not to share breastmilk with infant during treatment and for 1 month after the last dose
Programmatic & Administrative Requirements
- Provider and pharmacy must be certified in the VANFLYTA Risk Evaluation and Mitigation Strategy (REMS) restricted access program
- Prescribed and monitored by a VA or VA Community Care hematologist/oncologist