Keeping a balance in chronic lymphocytic leukemia (CLL) patients taking ibrutinib: ibrutinib-associated adverse events and their management based on drug interactions

Expert Rev Hematol. 2021 Sep;14(9):819-830. doi: 10.1080/17474086.2021.1967139. Epub 2021 Aug 22.

Abstract

Introduction: Ibrutinib is a highly effective drug for patients with chronic lymphocytic leukemia (CLL), and is well tolerated even by older patients and those unfit to receive conventional immuno-chemotherapy.

Areas covered: The occurrence of adverse events was revealed as a major cause of ibrutinib failure in the real-world. Ibrutinib-induced lymphocytosis carries the risk of an untimely interruption of therapy because it may be misinterpreted as disease progression. In addition, drug interactions can worsen ibrutinib-associated toxicities by increasing the plasma concentration of ibrutinib. In this review, we present a case of major hemorrhage and atrial fibrillation (AF) during ibrutinib use and summarize the adverse events associated with ibrutinib. Furthermore, the practical management of ibrutinib-associated toxicities was covered with reference to a drug interaction mechanism.

Expert opinion: Clinicians should examine the prescribed drugs prior to ibrutinib initiation and carefully monitor toxicities while taking ibrutinib. A reduced dose of ibrutinib with the concurrent use of CYP3A inhibitors such as antifungal agents could be an attractive strategy to reduce toxicities and may confer financial benefits. Reducing unexpected toxicities is as significant as achieving treatment response in the era of life-long therapy with ibrutinib in patients with CLL.

Keywords: Chronic lymphocytic leukemia (CLL); atrial fibrillation (AF); coronavirus disease (COVID-19); dose modification strategy; drug interaction; hemorrhage; ibrutinib; invasive fungal infection; lymphocytosis.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Adenine / therapeutic use
  • Aged
  • COVID-19 / complications
  • Disease Management
  • Drug Interactions
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Drug-Related Side Effects and Adverse Reactions / therapy
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / complications
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Male
  • Piperidines / adverse effects
  • Piperidines / pharmacology
  • Piperidines / therapeutic use*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*

Substances

  • Piperidines
  • Protein Kinase Inhibitors
  • ibrutinib
  • Adenine