B cell receptor inhibition as a target for CLL therapy

Deepa Jeyakumar; Susan O'Brien

doi:10.1016/j.beha.2016.08.004

B cell receptor inhibition as a target for CLL therapy

Best Pract Res Clin Haematol. 2016 Mar;29(1):2-14. doi: 10.1016/j.beha.2016.08.004. Epub 2016 Aug 11.

Authors

Deepa Jeyakumar¹, Susan O'Brien²

Affiliations

¹ 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.
² 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.

PMID: 27742069
DOI: 10.1016/j.beha.2016.08.004

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.

Keywords: Bruton's tyrosine kinase and phosphatidylinositol 3- kinase pathways; Chronic lymphocytic leukemia.

Publication types

Review

MeSH terms

Adenine / analogs & derivatives
Agammaglobulinaemia Tyrosine Kinase
Age Factors
Atrial Fibrillation / chemically induced
Atrial Fibrillation / immunology
Diarrhea / chemically induced
Diarrhea / immunology
Hemorrhage / chemically induced
Hemorrhage / immunology
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
Leukemia, Lymphocytic, Chronic, B-Cell / immunology
Lymphocytosis / chemically induced
Lymphocytosis / immunology
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / immunology
Phosphatidylinositol 3-Kinases / immunology
Phosphoinositide-3 Kinase Inhibitors
Piperidines
Pneumonia / chemically induced
Pneumonia / immunology
Protein-Tyrosine Kinases / antagonists & inhibitors
Protein-Tyrosine Kinases / immunology
Purines / adverse effects
Purines / therapeutic use*
Pyrazoles / adverse effects
Pyrazoles / therapeutic use*
Pyrimidines / adverse effects
Pyrimidines / therapeutic use*
Quinazolinones / adverse effects
Quinazolinones / therapeutic use*
Receptors, Antigen, B-Cell / antagonists & inhibitors*
Receptors, Antigen, B-Cell / immunology

Substances

Neoplasm Proteins
Phosphoinositide-3 Kinase Inhibitors
Piperidines
Purines
Pyrazoles
Pyrimidines
Quinazolinones
Receptors, Antigen, B-Cell
ibrutinib
Protein-Tyrosine Kinases
Agammaglobulinaemia Tyrosine Kinase
Adenine
idelalisib