Dr. Hill on the Potential Utility of Next-Generation PI3K Inhibitors in CLL

Brian T. Hill, MD, PhD, director, Lymphoid Malignancies Program, staff physician, Taussig Cancer Institute, chairman, Pharmacy and Therapeutics Committee, Department of Hematology and Medical Oncology, co-director, Lymphoid Malignancies Center of Excellence, Cleveland Clinic, associate professor, Cleveland Clinic Lerner College of Medicine, member, Case Comprehensive Cancer Center, assistant professor, Department of Medicine, School of Medicine, Case Western Reserve University, discusses the potential utility of next-generation PI3K inhibitors in chronic lymphocytic leukemia (CLL).

PI3K inhibitors are an active class of agents that can block B-cell receptor signaling in B-cell malignancies like CLL, Hill says. However, the development of PI3K inhibitors as standard options in CLL has been hindered by treatment-related toxicities. With prolonged dosing, PI3K inhibitors are associated with adverse effects including colitis, pneumonitis, and liver toxicities, Hill explains.

Notably, the newer-generation PI3K inhibitor umbralisib (Ukoniq) appears to cause lower rates of these toxicities compared with earlier-generation PI3K inhibitors, Hill explains. However, on February 3, 2022, the FDA announced that they are investigating umbralisib after initial data from the phase 3 UNITY-CLL trial (NCT02612311) revealed a potential increased risk of death in patients with CLL who received umbralisib.