Prospect & progress of venetoclax in treating chronic lymphocytic leukemia

Abstract

ABSTRACTIntroduction: Chronic Lymphocytic Leukemia (CLL) is characterized by the overexpression of BCL2, a pro-survival protein responsible for impaired apoptosis, tumor initiation, disease progression, and drug resistance. Venetoclax is a potent, second generation, orally bioavailable, BCL2 inhibitor.Areas covered: In early phase clinical trials, venetoclax has demonstrated remarkable activity in heavily pre-treated patients and those with poor prognostic features. Furthermore, it has shown efficacy and safety when combined with immunotherapy and chemotherapy, which has prompted phase III investigation. The most common adverse events are related to myelosuppression, infection, and diarrhea. Tumor lysis syndrome is the most concerning adverse event associated with venetoclax, but can be mitigated with risk-adapted prophylaxis.Expert opinion: The treatment landscape for CLL is evolving from chemoimmunotherapy to involve targeted biologic therapies, based on a greater understanding of the pathogenesis of this disease. Venetoclax provides an effective alternative to BCR pathway antagonists, with a distinct mechanism of action and adverse event profile.