Venetoclax in the Treatment of Chronic Lymphocytic Leukemia: Evidence, Expectations, and Future Prospects.

ABSTRACT

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the western adult population; it is also prevalent worldwide. The B cell lymphoma-2 (BCL-2) family proteins play a key role in regulating intrinsic apoptosis and, in many cancers, are the main culprits behind tumor survival and therapy resistance. Hence, the role of BCL-2 inhibitors is very beneficial in the treatment of CLL. Venetoclax is the first selective, orally bioavailable BCL-2 inhibitor. This review article discusses factors such as the pharmacokinetics, pharmacodynamics, acquired resistance to venetoclax, responders vs. non-responders in venetoclax monotherapy, and the synergistic role of venetoclax with other drugs in detail. Venetoclax is the first BH3 mimetic drug and selective BCL-2 inhibitor that has received FDA approval. This drug has proved to provide good therapeutic responses in CLL patients irrespective of the presence of adverse clinical or genetic features, including in patients with relapsed or refractory forms of CLL. We anticipate that novel combination therapies, including venetoclax and immunotherapy, will further alter the treatment landscape for patients with relapsed CLL, particularly for those with deletion 17p (del 17p) CLL, which carries a very poor prognosis.