How is Venclexta (venetoclax) used for AML?

When used to treat AML (acute myeloid leukemia) Venclexta is given as an increasing dose for the first few days, with the maintenance dose starting on the fourth day. The exact maintenance dose depends on the combination agent used, which is usually either azacytidine, decitabine, or low-dose cytarabine. For example:

• Day 1: Venclexta 100mg once daily
• Day 2: Venclexta 200mg once daily
• Day 3: Venclexta 400mg once daily
• Day 4 onwards: Venclexta 400mg once daily in combination with azacytidine or decitabine OR Venclexta 600mg once daily in combination with low-dose cytarabine.

Venclexta is continued on a once-daily dosing cycle at these dosages until disease progression or unacceptable toxicity is observed. Venclexta should be taken with food and at approximately the same time each day. Tablets should be swallowed whole and not crushed, chewed, or broken before swallowing.

Venclexta (venetoclax) is approved to treat AML in adults aged 75 years or older, or in those with other medical conditions that prevent the use of intensive induction chemotherapy.

Note that Venclexta has a different dosage schedule when used to treat CLL (chronic lymphocytic leukemia) and SLL (small lymphocytic lymphoma).

How does Venclexta work?

Venclexta works by inhibiting BCL-2, which is a group of proteins that are responsible for regulating cell death by either inhibiting or inducing apoptosis. Apoptosis is an ordered form of cell death in which the contents of the cell are “packaged” for collection by immune cells. It is different from the way cells die due to an injury.

In certain cancers, such as CLL (chronic lymphocytic leukemia) and AML (acute myeloid leukemia) there is an abundance of BCL-2 on the surface of CLL and AML cells. This overexpression of BCL-2 allows tumor cells to survive for longer and has been associated with resistance to chemotherapy treatments. Laboratory research has shown that Venclexta binds to this protein and kills cancerous CLL and AML lymphocytes.