Pre-existing cardiovascular disease increases risk of atrial arrhythmia and mortality in cancer patients treated with Ibrutinib

Abstract

Background Ibrutinib 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. Objective This study examined whether patients with pre-existing CVD are at a higher risk for developing atrial arrhythmias compared to those without prior CVD. Methods A 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. Results Patients 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. Conclusions Pre-existing cardiovascular disease was associated with significantly higher rates of atrial arrhythmia and mortality in patients with hematological malignancies managed with ibrutinib.

Cardiotoxicity from Bruton tyrosine kinase inhibitors (BTKi) – an analysis of an administrative health claims database

“…In a meta-analysis of four randomized clinical trials of patients with CLL, SLL, and mantle cell lymphoma treated with ibrutinib vs non-ibrutinib therapy, the pooled incidence rate of AF in the ibrutinib group was 3.3 per 100 years compared to 0.84 per 100 person years in the nonibrutinib group [21]. Avalon JC et al also found that pre-existing cardiovascular disease was associated with a signi cantly higher rates of atrial brillation/arrhythmias as well as mortality in those receiving treatment with ibrutinib [22].…”

Ibrutinib Is Associated With Increased Cardiovascular Events and Major Bleeding in Older CLL Patients

“…A single-center retrospective review of new onset AF in 217 ibrutinib-treated patients identified a 3-fold increased risk of AF and increased adjusted all-cause mortality in patients with prior coronary artery disease, congestive heart failure, pulmonary hypertension, moderate valvular heart disease, and cardiac device implantation. 25 It would be prudent to evaluate all CLL patients for prior cardiac disease before initiating ibrutinib.…”

A real‐world study to assess the association of cardiovascular adverse events (CVAEs) with ibrutinib as first‐line (1L) treatment for patients with chronic lymphocytic leukaemia (CLL) in the United States

“…A 2021 retrospective chart review from a single institution investigated whether patients with pre‐existing CVD had a higher likelihood of developing new AF than those with no prior CVD, following treatment with ibrutinib [ 31 ]. It was found that patients with prior CVD were 2.91 times more likely to develop AF than those without prior CVD, although this study was limited by its small sample size, and the sample of patients came from a single institution.…”