Venclyxto

Venclyxto is the brand name for venetoclax, an oral small-molecule anti-cancer drug that selectively inhibits BCL-2, a protein that helps certain cancer cells survive by blocking programmed cell death. By inhibiting BCL-2, venetoclax promotes apoptosis in malignant B cells and other cells dependent on BCL-2 for survival.

Mechanism of action: Venetoclax binds to the BCL-2 protein, releasing pro-apoptotic signals and triggering cell death in affected leukemic and lymphoid cells. It is considered a targeted therapy for B-cell malignancies when BCL-2 is a key survival factor.

Medical uses: In the United States, venetoclax is approved for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with or without 17p deletion, including relapsed or refractory disease, and in combination with rituximab for certain CLL/SLL cases. It is also approved for acute myeloid leukemia (AML) in adults, in combination with azacitidine, decitabine, or low-dose cytarabine for newly diagnosed patients ineligible for intensive chemotherapy. Regulatory approvals and specific indications vary by country and over time.

Administration and dosing: Venclyxto is taken as oral tablets. Dosing typically involves a ramp-up period over several weeks to reduce the risk of tumor lysis syndrome, with the exact regimen depending on the indication and combination therapy. Patients often receive prophylaxis for tumor lysis syndrome and regular monitoring of blood counts and organ function.

Safety and precautions: Common adverse effects include neutropenia, anemia, thrombocytopenia, nausea, diarrhea, and fatigue. Tumor lysis syndrome is a major consideration during initiation and requires appropriate monitoring and preventive measures. Venetoclax interacts with certain drugs, especially strong CYP3A inhibitors or inducers, necessitating dose adjustments. Use in pregnancy is generally avoided unless clearly needed.

Regulatory status: Venetoclax was developed by AbbVie and Genentech and has received regulatory approvals from agencies such as the FDA and EMA for multiple hematologic malignancies.