title: B cell receptor inhibition as a target for CLL therapy.
abstract: Inhibitors of the B cell receptor (BCR) represent an attractive therapeutic option for patients with chronic lymphocytic leukemia. Recently approved inhibitors of Bruton's tyrosine kinase (ibrutinib) and phosphatidylinositol 3-kinase (idelalisib), are promising agents because they are generally well tolerated and highly effective. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (and infections) associated with chemoimmunotherapy. As a class of medications, BCR inhibitors have some unique side effects including redistribution lymphocytosis. Ibrutinib has specific toxicities including increased risk for bleeding and atrial fibrillation. Idelalisib also has some unique toxicities consisting of transaminitis, diarrhea and pneumonitis. Ongoing clinical trials are evaluating these agents in combination with antibodies, chemotherapy and other small molecules.
authors.affiliation: Chao Family Comprehensive Cancer Center, Division of Hematology Oncology, Department of Medicine, University of California, Irvine, 101 The City Drive South, Building 56, Orange, CA 92868, USA. Electronic address: djeyakum@uci.edu.
authors.forename: Deepa
authors.initials: D
authors.lastname: Jeyakumar
authors.affiliation: Chao Family Comprehensive Cancer Center, Division of Hematology Oncology, Department of Medicine, University of California, Irvine, 101 The City Drive South, Building 56, Orange, CA 92868, USA. Electronic address: obrien@uci.edu.
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000367:Age Factors; D001281:Atrial Fibrillation / Q000139:chemically induced / Q000276:immunology; D003967:Diarrhea / Q000139:chemically induced / Q000276:immunology; D006470:Hemorrhage / Q000139:chemically induced / Q000276:immunology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology; D008218:Lymphocytosis / Q000139:chemically induced / Q000276:immunology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010880:Piperidines; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000276:immunology; D011687:Purines / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D052999:Quinazolinones / Q000009:adverse effects / Q000627:therapeutic use*; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000225:Adenine; D000077329:Agammaglobulinaemia Tyrosine Kinase; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010880:Piperidines; D011505:Protein-Tyrosine Kinases; D011687:Purines; D011720:Pyrazoles; D011743:Pyrimidines; D052999:Quinazolinones; D011947:Receptors, Antigen, B-Cell; C551803:ibrutinib; C552946:idelalisib
keywords: Bruton's tyrosine kinase and phosphatidylinositol 3- kinase pathways; Chronic lymphocytic leukemia