title: Venetoclax in Patients with Previously Treated Chronic Lymphocytic Leukemia.
abstract: Venetoclax is the first BCL2 inhibitor to enter routine clinical practice. It is an orally bioavailable small molecule that binds BCL2 very specifically. Acting as a pharmacologic mimic of the proteins that initiate apoptosis (a so-called BH3 mimetic), venetoclax rapidly induces apoptosis in chronic lymphocytic leukemia (CLL) cells, which express high levels of BCL2 and rely on it to maintain their survival. As a single agent, daily venetoclax treatment induced durable responses in 79% of patients with relapsed or refractory CLL or small lymphocytic lymphoma in a phase I study, including complete remissions in 20% of patients. Its use was approved by the FDA in April 2016 for patients with previously treated del(17p) CLL on the basis of a single-arm phase II trial demonstrating a 79% response rate and an estimated 1-year progression-free survival of 72% with 400 mg/day continuous therapy. This review focuses on venetoclax, its mechanism of action, pharmacology, and clinical trial data and seeks to place it in the context of rapid advances in therapy for patients with relapsed CLL, especially those with del(17p) CLL.Clin Cancer Res; 23(16); 4527-33. ©2017 AACR.
authors.affiliation: Integrated Department of Clinical Hematology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, Victoria, Australia. Roberts@wehi.edu.au.|Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia.|Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Roberts
authors.affiliation: Internal Medicine III, Ulm University, Ulm, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: Integrated Department of Clinical Hematology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, Victoria, Australia.|Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia.|Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.affiliation: Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: David C S
authors.initials: DCS
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D012074:Remission Induction; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; C579720:venetoclax