Dr. Brander on Targeted Agents in CLL

Danielle M. Brander, MD, assistant professor of medicine, Duke Cancer Institute, discusses targeted agents in chronic lymphocytic leukemia (CLL).

Targeted inhibitors in CLL and other B-cell lymphomas can be categorized by those that target important proteins along the B-cell receptor signaling pathway and those that induce apoptosis, explained Brander. Agents that target the B-cell receptor pathway include ibrutinib (Imbruvica) and acalabrutinib (Calquence); these target BTK specifically, which is one component of that pathway.

Other important components in that signaling pathway are PI3K inhibitors, adds Brander. Approved PI3K inhibitors include idelalisib (Zydelig) and duvelisib (Copiktra). PI3K inhibitors can be specific to PI3K-delta or PI3K-gamma, adds Brander. The type of isoform will determine whether the agent is tested in CLL versus other lymphomas.


Anti-apoptotic inhibitors include venetoclax (Venclexta), which is a specific BCL-2 inhibitor. In CLL, there is a defect in programmed cell death. The idea of an anti-apoptotic inhibitor is to tip the balance towards apoptosis, explains Brander. Ongoing trials with combination therapies may augment current approaches in targeting the B-cell receptor signaling pathway.