Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765)

Leuk Lymphoma. 2013 Nov;54(11):2385-91. doi: 10.3109/10428194.2013.777837. Epub 2013 Aug 28.

Abstract

Over the past 3 years, ibrutinib (PCI-32765) has emerged as a breakthrough in targeted therapy for patients with certain types of B cell malignancies. Early stage clinical trials found ibrutinib to be particularly active in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), providing the rationale for ongoing phase 3 trials. In contrast to conventional chemo-immunotherapy, ibrutinib is not myelosuppressive, and responses are not affected by disease features that predict failure to respond to or short remission durations after chemo-immunotherapy, such as del17p. In CLL, ibrutinib characteristically causes an early redistribution of tissue-resident CLL cells into the blood, with rapid resolution of enlarged lymph nodes, along with a surge in lymphocytosis. Later, after weeks to months of continuous ibrutinib therapy, the growth- and survival-inhibitory activities of ibrutinib result in the normalization of lymphocyte counts and remissions in a majority of patients. This review discusses the discovery, preclinical and clinical development of ibrutinib, its pathophysiological basis, and outlines perspectives for future use of ibrutinib.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / metabolism
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Drug Evaluation, Preclinical
  • Drug Resistance, Neoplasm
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Lymphoma, Mantle-Cell / drug therapy
  • Lymphoma, Mantle-Cell / metabolism
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction

Substances

  • PCI 32765
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • Receptors, Antigen, B-Cell
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase