title: Idelalisib: First-in-Class PI3K Delta Inhibitor for the Treatment of Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, and Follicular Lymphoma.
abstract: Idelalisib [Zydelig (Gilead Sciences, Inc.), also known as CAL-101 and GS-1101] was approved in 2014 in the United States and European Union for the treatment of three indolent B-cell neoplasms: relapsed/refractory chronic lymphocytic leukemia (CLL, in combination with rituximab), relapsed follicular lymphoma, and relapsed small lymphocytic lymphoma (as monotherapy). Furthermore, it was approved in the European Union as first-line therapy for poor-prognosis CLL with 17p deletions or TP53 mutations and in patients unsuitable for chemoimmunotherapy. Idelalisib is an orally bioavailable ATP-competitive kinase inhibitor that targets the PI3K p110 isoform δ (PI3Kδ) with high potency and selectivity. PI3Kδ is hyperactivated in B-cell malignancies and plays a pivotal role in the B-cell receptor pathway, a key oncogenic driver in B-cell malignancies. The near exclusive expression of the PI3Kδ isoform in hematopoietic cells and the selectivity of idelalisib for the PI3Kδ isoform are essential for its efficacy and tolerability, even in elderly patients unfit for chemotherapy. Idelalisib is the first PI3K inhibitor approved by the regulatory agencies; this approval will change the treatment landscape of indolent B-cell malignancies.
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Qingshan
authors: Q
authors: Yang
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Prexy
authors: P
authors: Modi
authors: Gilead Sciences, Seattle, Washington.
authors: Terry
authors: T
authors: Newcomb
authors: Gilead Sciences, Seattle, Washington.
authors: Christophe
authors: C
authors: Quéva
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas. vgandhi@mdanderson.org.
authors: Varsha
authors: V
authors: Gandhi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D058534:Class I Phosphatidylinositol 3-Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011687:Purines / Q000627:therapeutic use*; D052999:Quinazolinones / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011687:Purines; D052999:Quinazolinones; D058534:Class I Phosphatidylinositol 3-Kinases; C486018:PIK3CD protein, human; C552946:idelalisib