Management of adverse effects/toxicity of ibrutinib

Crit Rev Oncol Hematol. 2019 Apr:136:56-63. doi: 10.1016/j.critrevonc.2019.02.001. Epub 2019 Feb 10.

Abstract

Bruton tyrosine kinase signaling (BTK) is critical step for B-cell development and immunoglobulin synthesis. Ibrutinib is an orally bioavailable bruton tyrosine kinase inhibitor (BTKi) and forms an irreversible covalent bound to BTK at the Cysteine-481 residue. Ibrutinib has been approved by FDA for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia, marginal zone lymphoma and chronic graft-versus-host disease in allogeneic stem cell transplantation. Ibrutinib is generally well tolerated drug with rapid and durable responses but has some side events. The most common side effects are diarrhea, upper respiratory tract infection, bleeding, fatigue and cardiac side effects. These events are generally mild (grade I-II). However atrial fibrillation (AF) and bleeding are important and may be grade III or higher side effects require strict monitoring. Here side effects of ibrutinib have been summarized and important considerations in the management of these adverse events have been reviewed.

Keywords: Adverse effect; Atrial fibrillation; Bruising; Diarrhea; Ibrutinib; Infection; Skin reactions.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors
  • Atrial Fibrillation / chemically induced
  • Atrial Fibrillation / epidemiology
  • Atrial Fibrillation / therapy
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / therapy*
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Hemorrhage / therapy
  • Humans
  • Incidence
  • Leukemia / drug therapy
  • Leukemia / epidemiology
  • Lymphoma / drug therapy
  • Lymphoma / epidemiology
  • Piperidines
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazoles / adverse effects*
  • Pyrazoles / therapeutic use
  • Pyrimidines / adverse effects*
  • Pyrimidines / therapeutic use

Substances

  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Agammaglobulinaemia Tyrosine Kinase
  • Adenine