Exploring a Future for PI3K Inhibitors in Chronic Lymphocytic Leukemia

Purpose of Review Treatment for chronic lymphocytic leukemia has changed substantially in the past decade with an increasing shift towards use of targeted therapies, in particular agents targeting the B cell receptor pathway. Inhibition of PI3K, downstream of the B cell receptor pathway, represents an active therapeutic strategy in CLL. Here, we explore the relevance of PI3K inhibition in CLL, examine efficacy and toxicity of approved PI3K inhibitors in CLL, examine barriers to use of PI3K inhibitors, and explore strategies to optimize use of PI3K inhibitors in CLL. Recent Findings Current generation PI3K inhibitors are active agents in CLL but their use may be limited by immune-mediated toxicities. Clinical trials of next generation PI3K inhibitors are ongoing and early data suggests these agents are highly active with potentially differentiated toxicity profiles. Furthermore, alternative dosing schedules may reduce toxicities of these agents. Summary Inhibition of PI3K remains an important strategy in management of CLL and novel approaches to limit toxicities of PI3K inhibitors represent an important area of clinical research in CLL.