title: Venetoclax: A First-in-Class Oral BCL-2 Inhibitor for the Management of Lymphoid Malignancies.
abstract: OBJECTIVE
  To review the pharmacology, efficacy, and safety of venetoclax for treatment of lymphoid malignancies.
  
  
  METHODS
  A literature search was performed of PubMed and MEDLINE databases (2005 to September 2016), abstracts from the American Society of Hematology and the American Society of Clinical Oncology, and ongoing studies from clinicaltrials.gov. Searches were performed utilizing the following key terms: venetoclax, ABT-199, GDC-199, obatoclax, GX15-070, BCL-2 inhibitor, navitoclax, ABT-263, and Venclexta.
  
  
  METHODS
  Studies of pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of venetoclax in lymphoid malignancies were identified.
  
  
  RESULTS
  Recently, treatment of B-cell lymphoproliferative disorders has shifted from conventional cytotoxic chemotherapy to novel small-molecule inhibitors. The advent of recently Food and Drug Administration-approved oral agents ibrutinib and idelalisib has shifted the paradigm of chronic lymphocytic leukemia (CLL) treatment; however, complete remission is uncommon, and the outcome for patients progressing on these treatments remains poor. Attention has been focused on a novel target, the B-cell lymphoma-2 protein (BCL-2), which serves an essential role in regulation of apoptosis. Venetoclax has demonstrated efficacy in multiple subtypes of lymphoid malignancies, including patients with relapsed/refractory CLL harboring deletion 17p, with an overall response rate of nearly 80%. Venetoclax is generally well tolerated, with the significant adverse effect being tumor lysis syndrome, for which there are formal management recommendations.
  
  
  CONCLUSIONS
  Venetoclax has demonstrated promising results in relapsed/refractory lymphoid malignancies, with an acceptable adverse effect profile. As the role of BCL-2 inhibition in various malignancies becomes further elucidated, venetoclax may offer benefit to a myriad other patient populations.
authors.affiliation: 1 Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Amber C
authors.initials: AC
authors.lastname: King
authors.affiliation: 1 Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Peterson
authors.affiliation: 1 Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Troy Z
authors.initials: TZ
authors.lastname: Horvat
authors.affiliation: 1 Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Mabel
authors.initials: M
authors.lastname: Rodriguez
authors.affiliation: 1 Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Tang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D012074:Remission Induction; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D047368:Tumor Burden; D015275:Tumor Lysis Syndrome / Q000188:drug therapy / Q000209:etiology
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; C579720:venetoclax
keywords: basic pharmacology; hematology; leukemia; lymphoma; oncology