Dr. Smith on PI3K Inhibitors in CLL

Mitchell R. Smith, MD, PhD, division director, Cancer and Blood Disorders, and professor of medicine, GW Cancer Center, discusses the use of PI3K inhibitors in chronic lymphocytic leukemia (CLL).

PI3K inhibitors have become an important drug class in CLL, despite their reputation for having significant associated toxicities, says Smith. Idelalisib (Zydelig) was the first PI3K inhibitor to receive regulatory approval in 2014. In 2018, duvelisib (Copiktra) was also approved for the treatment of patients with relapsed/refractory disease. Duvelisib targets PI3K-delta and -gamma with a slightly different mechanism of action than idelalisib, explains Smith.

Umbralisib (TGR-1202) is another PI3K-delta inhibitor that also inhibits an enzyme called casein kinase-1ε. As opposed to earlier-generation PI3K inhibitors, umbralisib appears to be well tolerated. Copanlisib (Aliqopa) is another PI3K inhibitor that selectively inhibits p110-alpha and delta. Now that several active PI3K inhibitors have emerged in the space, the challenge will be determining which inhibitors to combine with other agents to optimize outcomes, concludes Smith.