💊 What is Venetoclax?
⚠️Venetoclax is a Bcl-2 inhibitor for treating chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML).
⚠️Venetoclax was approved by the US FDA in 2018 and 2021 by the European Medicine Agency (EMA) for the treatment of acute myeloid leukemia (AML) [citation].
A UK-led, international clinical trial VICTOR (Venetoclax or intensive chemotherapy for treatment of favorable risk AML), is investigating the efficacy of Venetoclax versus standard intense chemotherapy in over 60-year-olds with NPM1 mutated AML.
✍️ What are other names for Venetoclax?
Commercial names under which venetoclax is distributed are Venclexta and Venclyxto.
🧬 When is Venetoclax used?
⚠️ As already mentioned, Venetoclax is used for the treatment of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or acute myeloid leukemia (AML).
Venetoclax is indicated for newly diagnosed patients, especially for older (>75) or ineligible for intensive CTX in combination with hypomethylating agents (HMA) or low-dose cytarabine (LDAC) [citation].
⚠️ Venetoclax is used in AML patients with mutated NPM1.
Further research should be directed toward patients who do not fit this type of therapy.
Furthermore, Venetoclax, combined with FLT3 inhibitors, in patients with mutations on NPM1 mutated AML that are co-mutated with FLT3 mutations [citation].
🏭 Who produces Venetoclax?
Venclexta is manufactured by AbbVie Inc., and it is marketed by both Abbvie and Genentech USA, which is a member of the Roche Group [citation].
💊 How does Venetoclax work? What is a mode of action for Venetoclax?
⚠️ As mentioned above, venetoclax is a Bcl-2 inhibitor that works by blocking the action of Bcl-2 that helps cancer cells survive [citation].
Venetoclax (VEN) plus azacitidine has become the first-line therapy for elderly patients with acute myeloid leukemia [citation].
⚠️ The main side effects of venetoclax plus hypomethylating agents (HMAs) are hematological, with about 40% of cases showing:
Cytopenias (cytopenia is a condition characterized by a lower than normal number of blood cells) and
about 30% grade 3 or higher infectious complications [citation].
Proteins in the B cell of chronic lymphocytic leukemia (CLL)/lymphoma 2 (Bcl-2) family are important regulators of the apoptotic (programmed cell death) process.
The selective inhibition of Bcl-2 by venetoclax enables therapeutic induction of apoptosis without the negative effect of thrombocytopenia. Venetoclax helps restore the process of apoptosis by binding directly to the Bcl-2 protein, displacing pro-apoptotic proteins, leading to mitochondrial outer membrane permeabilization and the activation of caspase enzymes [citation].
ℹ️ How is Venetoclax applied?
ℹ️ The FDA label indicates that venetoclax should be taken with food, 400 mg daily [citation]. Venetoclax is a cytochrome P450 3A4 (CYP3A4) substrate. Thus, its dose should be reduced by at least 75% when combined with posaconazole, a strong CYP3A4 inhibitor commonly used for antifungal prophylaxis in AML [citation].
ℹ️ In combination with Venetoclax with “5+2” induction chemotherapy (CAVEAT trial) followed by four consolidation cycles was found to be safe in fit older patients with AML [citation].