FDA Approves Vanflyta (quizartinib) for Newly Diagnosed FLT3-ITD-Positive AML in Adults

Not reported in label.

Vanflyta is indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)-positive as detected by an FDA-approved test. Limitations of Use: VANFLYTA is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with VANFLYTA in this setting has not been demonstrated.

Take VANFLYTA tablets orally once daily with or without food at approximately the same time each day. A treatment course consists of up to 2 cycles of VANFLYTA in combination with induction cytarabine and anthracycline, up to 4 cycles of VANFLYTA in combination with high-dose cytarabine consolidation, and up to 36 cycles of VANFLYTA as maintenance therapy or until disease progression or unacceptable toxicity. VANFLYTA maintenance therapy should be initiated following consolidation chemotherapy upon blood count recovery of absolute neutrophil count >500/mm3 and platelet count >50,000/mm3. Recommended dosage: Induction: 35.4 mg orally once daily for two weeks in each cycle (Days 8 to 21). Consolidation: 35.4 mg orally once daily for two weeks in each cycle (Days 6 to 19). Maintenance: Administer 26.5 mg orally once daily Days 1 through 14 of the first cycle if QTcF is less than or equal to 450 ms. Increase the dose to 53 mg once daily on Day 15 of the first cycle if QTcF is less than or equal to 450 ms. Maintain the 26.5 mg once daily dose if QTcF greater than 500 ms was observed during induction or consolidation. Duration: Once daily with no break between cycles for up to 36 cycles. For patients who proceed to hematopoietic stem cell transplantation (HSCT), VANFLYTA should be stopped 7 days before the start of a conditioning regimen. If a dose is vomited, do not administer a replacement dose; wait until the next scheduled dose. If a dose is missed, administer as soon as possible on the same day and return to the usual schedule the next day; do not take two doses on the same day.

Trial data not available in label.

Initiate VANFLYTA only if QTcF is less than or equal to 450 ms. During induction and consolidation, perform ECGs prior to initiation and then once weekly during VANFLYTA treatment or more frequently as clinically indicated. During maintenance, perform ECGs prior to initiation, once weekly for at least the first month following dose initiation and escalation, and thereafter as clinically indicated. Escalate the dose only if QTcF is less than or equal to 450 ms. Correct electrolyte abnormalities (hypokalemia and hypomagnesemia), and if possible, avoid concomitant administration of drugs that prolong the QT interval. Dosage modifications for adverse reactions: QTcF between 450 ms and 480 ms (Grade 1): Continue VANFLYTA dose. QTcF between 481 ms and 500 ms (Grade 2): Reduce the dose of VANFLYTA without interruption. Resume VANFLYTA at the previous dose in the next cycle if QTcF has decreased to less than 450 ms. Monitor the patient closely for QT prolongation during the first cycle at the increased dose. QTcF greater than 500 ms (Grade 3): Interrupt VANFLYTA. Resume VANFLYTA at a reduced dose when QTcF returns to less than 450 ms.

Vanflyta is used in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for adult patients with newly diagnosed FLT3-ITD-positive AML. It is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation.