title: Ibrutinib for treatment of chronic lymphocytic leukemia.
abstract: OBJECTIVE
  The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of ibrutinib are described.
  
  
  CONCLUSIONS
  Ibrutinib is a first-in-class oral inhibitor of Bruton tyrosine kinase (BTK) approved for treatment of relapsed chronic lymphocytic leukemia (CLL). Ibrutinib blocks downstream signaling of the B-cell receptor, disrupting stromal microenvironment interactions and B-cell cytokine signaling. BTK inhibition has been shown to be effective in relapsed or refractory CLL. A recent Phase III study evaluated ibrutinib (420 mg daily) versus ofatumumab (consistent with labeling) in relapsed or refractory CLL with a primary endpoint of progression free survival (PFS, n = 391). After a median follow-up period of 9.4 months, a PFS was not attained in ibrutinib-treated individuals with and without deletion 17p. In contrast, ofatumumab-treated individuals experienced a PFS of 8.1 months and those with deletion 17p experienced a PFS of 5.8 months. Major hemorrhage was reported in 2 (1%) patients treated with ibrutinib, and a total of 8 (4%) patients discontinued treatment due to toxicity or adverse reactions. Partial response or partial response with lymphocytosis was achieved in 63% of ibrutinib-treated individuals as determined by independent assessments. Overall, ibrutinib reduced the rate of mortality by 57%.
  
  
  CONCLUSIONS
  Ibrutinib is a first-in-class, orally active, irreversible BTK inhibitor with a novel mechanism of action. This unique mechanism of action and high overall response rates observed in clinical trials make ibrutinib an attractive second-line option in patients who have disease progression while receiving monoclonal antibody therapy or chemoimmunotherapy.
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. cvela20@gmail.com.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Vela
authors.affiliation: University of Arizona Cancer Center, Tuscon, AZ.
authors.forename: Ali
authors.initials: A
authors.lastname: McBride
authors.affiliation: Division of Hematology, Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Solove Research Institute, Columbus, OH.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Jaglowski
authors.affiliation: Division of Hematology, Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Solove Research Institute, Columbus, OH.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Andritsos
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D002986:Clinical Trials as Topic / Q000379:methods; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011720:Pyrazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D000225:Adenine