Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia and lymphoma

Clin Adv Hematol Oncol. 2016 Jul;14(7):543-54.

Abstract

The development of Bruton's tyrosine kinase (BTK) inhibitors and their introduction into clinical practice represent a major advance in the treatment of chronic lymphocytic leukemia (CLL) and other B-cell lymphomas. Although ibrutinib is the only BTK inhibitor that has been approved by the US Food and Drug Administration, several others are under investigation. Ibrutinib is currently approved for use in relapsed/refractory CLL, CLL with 17p deletion (del[17p]), relapsed or refractory mantle cell lymphoma, and Waldenström macroglobulinemia. Although it is clear that ibrutinib has altered treatment paradigms and outcomes in these diseases, several questions remain regarding (1) its role in frontline vs salvage therapy; (2) its use as a single agent vs in combination with biologic agents, other small molecules, or traditional chemoimmunotherapy; (3) the optimal duration of treatment; and (4) the treatment of patients who cannot tolerate or have disease resistant to ibrutinib. Because sparse clinical data are available on other BTK inhibitors, it is unclear at present whether their clinical efficacy and toxicity will differ from those of ibrutinib.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Neoplasm Staging
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Recurrence
  • Treatment Outcome

Substances

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