Venetoclax — Drug Monograph

Brand names: Venclexta

Drug class: BCL-2 Inhibitor

Mechanism of Action

Selective, orally bioavailable inhibitor of the anti-apoptotic protein BCL-2 (B-cell lymphoma-2). BCL-2 overexpression in CLL and other hematologic malignancies prevents apoptosis by sequestering pro-apoptotic proteins (BAX, BAK). Venetoclax binds BCL-2 directly, releasing pro-apoptotic proteins and restoring the intrinsic apoptosis pathway.

FDA Indications

• CLL/SLL — first-line (with obinutuzumab) or relapsed/refractory (with rituximab or monotherapy)
• AML — first-line in adults ≥75 years or unfit for intensive induction chemotherapy (in combination with azacitidine, decitabine, or low-dose cytarabine)

Common Side Effects

• Nausea, diarrhea
• Neutropenia
• Fatigue
• Upper respiratory tract infections
• Anemia, thrombocytopenia

Clinical Pearl

CLL assessment for TLS risk before venetoclax: low risk (lymphocytes <25K and all lymph nodes <5 cm) — outpatient ramp-up with oral hydration; medium risk (any LN 5–10 cm) — consider hospitalization for first few doses; high risk (any LN ≥10 cm, or LN ≥5 cm with lymphocytes ≥25K) — hospitalization for ramp-up. Rasburicase can be used for established hyperuricemia.

Related Therapies & Mechanisms

• Acalabrutinib (Calquence) — Lymphoma
• Bendamustine (Treanda) — Lymphoma
• Brexucabtagene autoleucel (Tecartus) — Lymphoma
• Cyclophosphamide (Cytoxan) — Lymphoma