title: Ibrutinib as a Bruton Kinase Inhibitor in the Management of Chronic Lymphocytic Leukemia: A New Agent With Great Promise.
abstract: The recent discovery of the role of the B-cell antigen receptor (BCR) signaling pathway in the propagation and maintenance of both normal B-cell function and in B-cell malignancies has highlighted the importance of many protein kinases involved in BCR signal propagation. Considerable research attention has focused on the Bruton tyrosine kinase (BTK) as a potential therapeutic target in B-cell malignancies. Treatment paradigms including ibrutinib, a potent inhibitor of the BTK recently approved by the US Food and Drug Administration, have significantly improved disease outcome among high-risk and relapsed/refractory cases of chronic lymphocytic leukemia. This has provided additional treatment options, especially among the elderly, where improved disease response has been accompanied by more manageable treatment-associated toxicity than commonly found with chemoimmunotherapy. In this review, we provide a synopsis of the current data on the efficacy and clinical utilization of ibrutinib and management of its resistance in the treatment of chronic lymphocytic leukemia.
authors.affiliation: Department of Hematology and Oncology, Oakland University, William Beaumont School of Medicine, William Beaumont Health System, Royal Oak, MI. Electronic address: Ogunleye.Foluso@beaumont.edu.
authors.forename: Ogunleye
authors.initials: O
authors.lastname: Foluso
authors.affiliation: Department of Hematology and Oncology, Oakland University, William Beaumont School of Medicine, William Beaumont Health System, Royal Oak, MI.
authors.forename: Alexander
authors.initials: A
authors.lastname: Glick
authors.affiliation: Department of Hematology and Oncology, Oakland University, William Beaumont School of Medicine, William Beaumont Health System, Royal Oak, MI.
authors.forename: Michael
authors.initials: M
authors.lastname: Stender
authors.affiliation: Department of Hematology and Oncology, Oakland University, William Beaumont School of Medicine, William Beaumont Health System, Royal Oak, MI.
authors.forename: Ishmael
authors.initials: I
authors.lastname: Jaiyesimi
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000378:metabolism; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D011947:Receptors, Antigen, B-Cell; C551803:ibrutinib; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D000225:Adenine
keywords: Antineoplastic agents; Clinical trials; Drug therapy; Protein tyrosine kinase antagonists/inhibitors; Review