William G. Wierda, MD, PhD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses novel therapies in patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

Chemoimmunotherapy regimens have long been the standard of care in the frontline setting, and things get a little more challenging when talking about novel treatment strategies, such as ibrutinib (Imbruvica)-based therapies, Wierda says. However, recent encouraging data with the BTK inhibitor in combination with other agents suggest this could be a new frontline standard approach. For patients who progress on frontline ibrutinib or treatment with a CD20-directed antibody, there are a couple of options. For example, there are data showing that the BLC-2 inhibitor venetoclax (Venclexta) has a reasonable response rate in patients with CLL who progress on treatment with ibrutinib.

There are also data suggesting that the combination of a PI3K inhibitor and a CD20-directed monoclonal antibody has promise in the second-line setting. PI3K inhibitors have some added toxicity; therefore, Wierda suggests the use of venetoclax following ibrutinib. Other strategies like reversible BTK inhibitors and chimeric antigen receptor T-cell therapy are being explored.