Quizartinib

Approved Uses

Quizartinib is used to treat newly diagnosed acute myeloid leukemia (AML), which is a fast-growing cancer of the blood and bone marrow. It is specifically indicated for adults whose cancer cells have a mutation in the FLT3 gene, specifically the internal tandem duplication (ITD) mutation.

Treatment Phases

This medication is used at different stages of the treatment process:

• Induction: It is used in combination with standard chemotherapy to help achieve remission.
• Consolidation: It is used with chemotherapy after remission to help prevent the cancer from returning.
• Maintenance: It is used alone as a long-term treatment after the initial phases of chemotherapy are finished.

A healthcare provider will perform a specific diagnostic test to confirm the presence of the FLT3-ITD mutation before prescribing this medicine. It is not intended for use in patients who do not have this specific genetic marker.

Targeting FLT3 Proteins

Quizartinib belongs to a class of medications called kinase inhibitors. It works by targeting and blocking a specific protein found on the surface of leukemia cells called Fms-like tyrosine kinase 3 (FLT3).

In a healthy body, the FLT3 protein helps regulate the production of blood cells. However, in some patients with acute myeloid leukemia (AML), the gene for this protein has a specific mutation called internal tandem duplication (ITD). This mutation causes the FLT3 protein to become overactive, sending constant signals to the leukemia cells to grow and divide uncontrollably.

How It Affects Cancer Cells

By binding to the mutated FLT3 protein, quizartinib interferes with these growth signals. This action helps to:

• Stop or slow the proliferation of cancerous white blood cells.
• Induce the death of leukemia cells that rely on the FLT3 signal to survive.

Because this medication targets a specific protein associated with a genetic mutation, it is considered a targeted therapy rather than a traditional chemotherapy that affects all rapidly dividing cells in the body.

Common Side Effects

• Nausea and vomiting
• Diarrhea or constipation
• Mouth sores or inflammation
• Stomach pain
• Fatigue or weakness
• Headache
• Fever
• Decreased appetite
• Muscle or joint pain
• Swelling in the arms or legs

Serious Side Effects

Seek medical attention immediately if you experience any of the following:

• Signs of heart rhythm changes, such as a racing heartbeat, dizziness, or fainting
• Signs of infection, including fever, chills, or cough
• Unusual bleeding or bruising
• Shortness of breath
• Severe skin reactions

This medication can cause significant changes in your blood cell counts, including low white blood cells, red blood cells, and platelets. Your healthcare team will perform regular blood tests and heart monitoring while you are taking this drug.

Boxed Warning: Heart Rhythm Risks

Quizartinib can cause a serious heart condition known as QT prolongation, which affects the heart's electrical rhythm. This condition can lead to Torsades de Pointes, a life-threatening type of irregular heartbeat, or sudden cardiac arrest.

Vanflyta REMS Program

Because of the risk of serious heart rhythm problems, quizartinib is only available through a restricted program called the Vanflyta Risk Evaluation and Mitigation Strategy (REMS). Healthcare providers and pharmacies must be certified in this program to prescribe or dispense the medication.

Monitoring and Contraindications

Healthcare providers will monitor heart health using electrocardiograms (ECGs) before starting treatment, once a week during the first month, and periodically thereafter. Treatment should not be started or continued if certain heart rhythm measurements are too high.

Quizartinib should not be used by individuals with:

• Severe low potassium (hypokalemia)
• Severe low magnesium (hypomagnesemia)
• Long QT syndrome
• A history of certain serious heart rhythm issues, such as ventricular arrhythmias or Torsades de Pointes

Electrolyte Imbalance

Low levels of potassium or magnesium in the blood increase the risk of heart rhythm problems. These levels must be checked and corrected before starting quizartinib and monitored regularly during treatment.

Drug Interactions

Many other medications can interact with quizartinib, either by increasing its concentration in the body or by further increasing the risk of heart rhythm issues. This includes certain antibiotics, antifungals, and heart medications. It is important to review all current medications with a healthcare provider.

Pregnancy and Breastfeeding

Quizartinib can cause harm to an unborn baby. Effective birth control should be used during treatment and for at least seven months after the last dose for females, and four months for males with partners of reproductive potential. Breastfeeding is not recommended during treatment and for one month after the final dose.

Pregnancy

Quizartinib may cause fetal harm if taken during pregnancy. Animal studies indicate that the medication can lead to embryo-fetal toxicity, which may result in birth defects or pregnancy loss. Individuals who can become pregnant should typically have a pregnancy test to confirm they are not pregnant before starting this treatment.

Contraception Requirements

Because of the potential risks to a developing fetus, healthcare providers recommend strict adherence to birth control measures:

• Females: Use effective contraception during treatment and for 7 months after the final dose.
• Males: If you have a female partner who can become pregnant, use effective contraception during treatment and for 4 months after the final dose.

Breastfeeding

It is not known whether quizartinib passes into human breast milk. Because of the risk of serious adverse reactions in a nursing infant, breastfeeding is not recommended during treatment and for at least one month after the last dose. Patients should discuss the best way to feed their baby with a healthcare provider during this time.

Available Forms

Quizartinib is currently available in the following form:

• Oral Tablet: This medication is taken by mouth, usually once daily with or without food.

The tablets should be swallowed whole. Do not crush, chew, or break the tablets before swallowing.

FDA Approval and Indications

The U.S. Food and Drug Administration (FDA) approved quizartinib in July 2023. It is indicated for use in combination with standard cytarabine and anthracycline induction and cytarabine consolidation chemotherapy, followed by maintenance monotherapy, for adults with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)-positive.

The presence of the FLT3-ITD mutation must be confirmed by an FDA-approved diagnostic test before treatment begins. Quizartinib is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation.

Boxed Warning and REMS

Quizartinib carries a Boxed Warning, the FDA's most serious warning, regarding the risk of QT prolongation, torsades de pointes, and cardiac arrest. Because of these life-threatening cardiac risks, the drug is only available through a restricted program called the Vanflyta Risk Evaluation and Mitigation Strategy (REMS).

Requirements of the REMS program include:

• Healthcare providers who prescribe the medication must be certified in the program.
• Pharmacies must be certified and may only dispense the drug to patients who are enrolled.
• Healthcare settings must be certified to ensure appropriate monitoring and management of cardiac risks.

Pharmacogenomic Considerations

The FDA includes quizartinib in its table of pharmacogenomic biomarkers in drug labeling. The medication is specifically targeted for patients with the FLT3-ITD mutation, and its safety and efficacy have not been established in patients with other types of AML.

FDA Approval and Indications

The U.S. Food and Drug Administration (FDA) approved quizartinib in July 2023. It is specifically indicated for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) that tests positive for a genetic mutation known as FLT3 internal tandem duplication (ITD).

Quizartinib is approved for use in three distinct phases of AML treatment:

• Induction: Used in combination with standard cytarabine and anthracycline chemotherapy.
• Consolidation: Used in combination with cytarabine chemotherapy.
• Maintenance: Used as a single-agent therapy following consolidation chemotherapy.

The FDA requires that the FLT3-ITD mutation be confirmed by an approved diagnostic test before treatment begins. Quizartinib is not indicated as a standalone treatment for the induction or consolidation phases of therapy.