Idelalisib at the Crossroads of B-Cell Lymphoproliferative Disorders

Phosphatidylinositol 3-kinases (PI3Ks) are considered as lipid kinases that are very active in the pathobiology of lymphoproliferative disorders (LPDs). Idelalisib, a selective inhibitor of the delta isoform of PI3K, provides significant clinical efficacy and has an acceptable side-effect profile in the treatment of B-LPDs. The aim of this review is to outline the pharmacobiological basis of idelalisib that is located at the crossroads of B-LPDs. The PI3K signaling pathway with downstream targets including Akt is involved in hematologic malignancies and lymphomas. Idelalisib has been most widely studied in chronic lymphoid leukemia (CLL) and B-lymphoma. The activity of idelalisib in high-risk FL with early relapse following front line immunochemotherapy was recently shown. The unique immunological toxicity pattern of idelalisib was also decribed in this review. Further clinical investigations will help for the better selection of the subsets of the patients with B-LPD that would be best candidates for the clinical utilization of idelalisib. Other indications such as marginal zone lymphoma, mantle cell lymphoma, Waldenstrom's Macroglobulinemia and other B-cell disorders could likely to be expanded. Future clinical and experimental data combined with the next-generation genomics strategies and personalized medicine for the treatment of malignant disorders will enlightened us for better placement of idelalisib in the treatment algorithm of the patients