Ibrutinib and indolent B-cell lymphomas

Clin Lymphoma Myeloma Leuk. 2014 Aug;14(4):253-60. doi: 10.1016/j.clml.2013.11.005. Epub 2013 Nov 15.

Abstract

Most patients with indolent B-cell lymphomas fail to achieve complete remission with current treatment approaches and invariably relapse. During the past decade, innovative immunochemotherapy strategies have substantially improved disease control rates but not survival, thus providing the rationale for development of novel agents targeting dysregulated pathways that are operable in these hematological malignancies. Ibrutinib, a novel first-in-human Bruton's tyrosine kinase (BTK) inhibitor, has progressed into phase III trials after early-phase clinical studies demonstrated effective target inhibition, increased tumor response rates, and significant improvement in survival, particularly in patients with indolent B-cell lymphomas. Recently, the compound was designated a "breakthrough therapy" by the United States Food and Drug Administration for the treatment of patients with relapsed or refractory mantle cell lymphoma and Waldenström macroglobulinemia. This review summarizes recent achievements of ibrutinib, with a focus on its emerging role in the treatment of patients with indolent B-cell lymphoid malignancies.

Keywords: Bruton's tyrosine kinase; Chronic lymphocytic leukemia/small lymphocytic lymphoma; Follicular lymphoma; Mantle cell lymphoma; Non-Hodgkin lymphoma.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Humans
  • Lymphoma, B-Cell / drug therapy*
  • Piperidines
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Adenine