Shagun Arora, MD, assistant clinical professor at the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, discusses novel therapies in the treatment of patients with chronic lymphocytic leukemia (CLL).

There are 3 classes of therapy in CLL, explains Arora—–BTK inhibitors, PI3K-delta inhibitors, and BCL-2 inhibitors. Ibrutinib (Imbruvica) is a BTK inhibitor that was first approved in 2014 for patients who had received at least 1 prior therapy as well as those with a 17p deletion. In 2016, the label was expanded to include frontline use. The approval was based on data from the RESONATE-2 trial, which compared the BTK inhibitor with chlorambucil in 269 treatment-naïve patients with CLL or small lymphocytic lymphoma 65 years or older.

In an ongoing phase III study (NCT02477696; ACE-CL-006), ibrutinib is being compared head-to-head with the second-generation BTK inhibitor, acalabrutinib (Calquence) in previously treated patients. Acalabrutinib has not shown as severe of side effects as seen with ibrutinib, explains Arora. Based on the results of the trial, acalabrutinib may become a suitable frontline option for patients who cannot tolerate ibrutinib.