Abstract
For the treatment of mature B cell malignancies including chronic lymphocytic leukemia (CLL), the last 5 years has brought major advances in the application of targeted therapies. Whilst monoclonal anti-CD20 agents such as rituximab have a central role in combination with traditional cytotoxic therapy, their combination with novel agents that target the B cell receptor signaling pathway and other intracellular mechanisms of B cell proliferation is a new approach to treatment. Venetoclax is a highly specific novel agent inhibiting the bcl-2 anti-apoptotic pathway and has potent activity in CLL. Its combination with rituximab results in deeper and more durable responses and this regimen is a valuable option in the treatment of relapsed or refractory CLL including adverse prognostic variants such as cases that are fludarabine refractory or harbor the 17p chromosomal deletion. This review centers on the use of venetoclax and rituximab in relapsed or refractory CLL.