BCL-2 as a therapeutic target in chronic lymphocytic leukemia.

Venetoclax (formerly ABT-199) was recently approved in the United States for the treatment of patients who have relapsed or refractory chronic lymphocytic leukemia (CLL) with the 17p deletion. Venetoclax has demonstrated marked activity as monotherapy as well as in combination with cytotoxic chemotherapies, B-cell receptor inhibitors, and anti-CD20 monoclonal antibodies across the spectrum of CLL. The potency of venetoclax has been associated with a unique ability to induce deep (minimal residual disease-negative) complete remissions that appear to be durable. Its toxicity profile includes manageable hematologic toxicities, as well as the potential for tumor lysis syndrome. Here, we review the BCL-2 pathway and the mechanism of action of BCL-2 inhibitors, the activity and safety profile of venetoclax, and the practical application of venetoclax in the management of patients with CLL.