Cardiotoxicity of BTK inhibitors: ibrutinib and beyond

Expert Rev Hematol. 2022 Apr;15(4):321-331. doi: 10.1080/17474086.2022.2067526. Epub 2022 Apr 22.

Abstract

Introduction: The development of Bruton<apos;>s Tyrosine Kinase (BTK) inhibitors has transformed the treatment of B-cell malignancies and other non-malignant conditions. Management of the unique cardiotoxic profile of these agents requires prompt recognition and a multi-disciplinary approach.

Areas covered: The increasing indications and addition of newer agents to clinical practice and emergence of BTK inhibitor-related cardiac adverse events have complicated the management decisions for utilization of this class of therapy. We review the incidence, mechanisms, and management approaches for BTK inhibitor-related atrial fibrillation, hypertension, and ventricular arrhythmias.

Expert opinion: The newer BTK inhibitor acalabrutinib represents a new standard of care in front-line chronic lymphocytic leukemia (CLL) given the results of the ELEVATE-RR trial demonstrating comparable efficacy and a more favorable toxicity profile especially with regard to cardiac adverse events as compared to ibrutinib. Often not recognized by clinicians, BTK inhibitor-induced hypertension is common and can be severe, requiring prompt recognition and initiation or adjustment of anti-hypertensive medications to prevent major adverse cardiac outcomes. Novel BTK inhibitors in development are being designed to overcome the patterns of resistance from first-generation agents and to minimize off-target kinase activity, with promising toxicity profiles in early trials.

Keywords: Acalabrutinib; atrial fibrillation; cardio-oncology; chronic lymphocytic leukemia; hypertension; ibrutinib; non-Hodgkin lymphoma; ventricular tachycardia; zanubrutinib.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase
  • Cardiotoxicity / drug therapy
  • Cardiotoxicity / etiology
  • Humans
  • Hypertension*
  • Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell* / pathology
  • Piperidines
  • Protein Kinase Inhibitors / adverse effects
  • Pyrimidines / adverse effects

Substances

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