Phosphatidylinositol 3 Kinase δ Inhibitors: Present and Future

Inhibitors of PI3Kδ hold great potential for the therapy of chronic lymphocytic leukemia and B-cell malignancies. After initially exciting efficacy results with idelalisib, the first-in-class inhibitor, the emergence of unexpected and unpredictable autoimmune toxicities, worse in less heavily treated and younger patients, has decreased the use of the currently available inhibitors. Newer drugs in development are attempting to reduce toxicity with novel schedules and/or combinations. This article reviews the clinical data on efficacy and toxicity across the class and discusses ongoing efforts to understand and mitigate the likely on-target autoimmune toxicity.