Cardiotoxicity of BTK inhibitors: ibrutinib and beyond

Bradley W. Christensen, Vlad G. Zaha, Farrukh T. Awan

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)321-331
Number of pages11
JournalExpert Review of Hematology
Volume15
Issue number4
DOIs
StatePublished - 2022
Externally publishedYes

Keywords

  • Acalabrutinib
  • atrial fibrillation
  • cardio-oncology
  • chronic lymphocytic leukemia
  • hypertension
  • ibrutinib
  • non-Hodgkin lymphoma
  • ventricular tachycardia
  • zanubrutinib

ASJC Scopus subject areas

  • Hematology

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