Abstract

BackgroundIbrutinib is a Bruton’s tyrosine kinase inhibitor used in the treatment of hematological malignancies. The most common cardiotoxicity associated with ibrutinib is atrial arrhythmia (atrial fibrillation and flutter). It is known that patients with cardiovascular disease (CVD) are at an increased risk for developing atrial arrhythmia. However, the rate of atrial arrhythmia in patients with pre-existing CVD treated with ibrutinib is unknown.ObjectiveThis study examined whether patients with pre-existing CVD are at a higher risk for developing atrial arrhythmias compared to those without prior CVD.MethodsA single-institution retrospective chart review of patients with no prior history of atrial arrhythmia treated with ibrutinib from 2012 to 2020 was performed. Patients were grouped into two cohorts: those with CVD (known history of coronary artery disease, heart failure, pulmonary hypertension, at least moderate valvular heart disease, or device implantation) and those without CVD. The primary outcome was incidence of atrial arrhythmia, and the secondary outcomes were all-cause mortality, risk of bleeding, and discontinuation of ibrutinib. The predictors of atrial arrhythmia (namely atrial fibrillation) were assessed using logistic regression. A Cox-Proportional Hazard model was created for mortality.ResultsPatients were followed for a median of 1.1 years. Among 217 patients treated with ibrutinib, the rate of new-onset atrial arrhythmia was nearly threefold higher in the cohort with CVD compared to the cohort without CVD (17% vs 7%, p = 0.02). Patients with CVD also demonstrated increased adjusted all-cause mortality (OR 1.9, 95% CI 1.06-3.41, p = 0.01) and decreased survival probability (43% vs 54%, p = 0.04) compared to those without CVD over the follow-up period. There were no differences in risk of bleeding or discontinuation between the two cohorts.ConclusionsPre-existing cardiovascular disease was associated with significantly higher rates of atrial arrhythmia and mortality in patients with hematological malignancies managed with ibrutinib.

Highlights

  • Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor that is commonly used for the treatment of various hematological malignancies since first approved in November 2013 [1]

  • Among 217 patients treated with ibrutinib, the rate of newonset atrial arrhythmia was nearly threefold higher in the cohort with cardiovascular disease (CVD) compared to the cohort without CVD (17% vs 7%, p = 0.02)

  • Pre-existing cardiovascular disease was associated with significantly higher rates of atrial arrhythmia and mortality in patients with hematological malignancies managed with ibrutinib

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Summary

Introduction

Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor that is commonly used for the treatment of various hematological malignancies since first approved in November 2013 [1]. Till date, this drug has been approved and indicated for treatment of chronic lymphocytic leukemia. Common cardiac arrhythmias that have been associated with ibrutinib include ventricular tachyarrhythmias and, most commonly, atrial fibrillation. Ibrutinib has an off-target inhibitory effect on Tec protein tyrosine kinase (TEC) Both BTK and TEC are expressed in cardiac tissue with an increased concentration in atrial tissue [15,16,17]. The rate of atrial arrhythmia in patients with pre-existing CVD treated with ibrutinib is unknown

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