Ibrutinib in B lymphoid malignancies

Expert Opin Pharmacother. 2015;16(12):1879-87. doi: 10.1517/14656566.2015.1067302. Epub 2015 Jul 13.

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords: B cell receptor; bruton’s tyrosine kinase; chronic lymphocytic leukemia; non-Hodgkin lymphoma.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / drug therapy*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • Waldenstrom Macroglobulinemia / drug therapy*

Substances

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