title: Idelalisib: Targeting the PI3 Kinase Pathway in Non-Hodgkin Lymphoma.
abstract: Based on substantial preclinical rationale, the restricted hematopoietic expression of the δ isoform of the phosphatidylinositol 3-kinase represents an attractive therapeutic target in B-cell malignancies. Its inhibition results in a direct antiproliferative effect on tumor cells as well as several modifications of their cellular microenvironment, all accounting for the potential therapeutic interest. Idelalisib, the first-in-class phosphatidylinositol 3-kinase δ-specific inhibitor, was developed in patients with B-cell lymphomas and chronic lymphocytic leukemia. Early clinical results demonstrated a potent antitumor effect across different subtypes of indolent and mantle cell lymphomas (where response duration was short). Adverse events, including transaminitis, neutropenia, pneumonitis, and diarrhea, were observed. A pivotal phase II study in patients with double refractory disease showed a 57% response rate, with response lasting for about 1 year, leading to market approval of the drug in the United States and Europe. Further developments of idelalisib combinations will contribute to delineate the position of this drug in the therapeutic strategy of indolent lymphomas.
authors: From the *Faculté de Médecine Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon-1; †Laboratoire d'Hématologie Biologique, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud; ‡INSERM U1052, Equipe "Clinical and Experimental Models of Lymphomagenesis," Cancer Research Center of Lyon; and §Unité de Pharmacie Clinique Oncologique, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon; ‖Université Claude Bernard Lyon-1, EMR 3738, Pierre-Bénite; and ¶Service d'Hématologie Clinique, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon, France.
authors: Pierre
authors: P
authors: Sujobert
authors: Catherine
authors: C
authors: Rioufol
authors: Gilles A
authors: GA
authors: Salles
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D006801:Humans; D007527:Isoenzymes; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use*; D052999:Quinazolinones / Q000494:pharmacology / Q000627:therapeutic use*; D012008:Recurrence; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines; D052999:Quinazolinones; C552946:idelalisib