title: Ibrutinib in B lymphoid malignancies.
abstract: BACKGROUND
  Most lymphomas and lymphoid leukemias are of B cell origin. Indolent B cell lymphomas, most commonly follicular lymphoma but including Waldenstrom's macroglobulinemia and mantle cell lymphoma, as well as chronic lymphocytic leukemia, are incurable with standard therapy. New treatments are needed. Survival of normal and many abnormal B cells depends on signals through the B-cell receptor, and a key element of this pathway is Bruton's tyrosine kinase (BTK). The oral BTK inhibitor ibrutinib is already US FDA approved in four different indications based on marked treatment benefit in indolent B cell lymphoma/leukemia.
  
  
  METHODS
  This review covers the clinical pharmacology of ibrutinib, its efficacy in clinical trials in chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia, as well as safety and toxicity. Future directions are discussed.
  
  
  CONCLUSIONS
  Ibrutinib is a well-tolerated once-daily oral BTK inhibitor with impressive activity in treating indolent B cell lymphoproliferative disorders. As a single agent, it is already altering treatment paradigms in its approved indications. Ongoing studies will determine its movement to the front-line setting in these and other B cell disorders, as well as combination approaches.
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, OH , USA +1 216 444 4366 ; +1 216 444 9464 ; smithm14@ccf.org.
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: Smith
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; 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
keywords: B cell receptor; bruton’s tyrosine kinase; chronic lymphocytic leukemia; non-Hodgkin lymphoma