Abstract 16653: Ventricular Arrhythmias With Ibrutinib Use: A Systematic Review and Meta-Analysis

Abstract

Introduction: Ibrutinib is a widely used treatment option for patients with chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. There is limited investigation on the relationship between ibrutinib and the development of ventricular arrhythmias. Hypothesis: We hypothesized that the incidence of ventricular arrhythmias in patients taking ibrutinib compared to the patients on other treatment regimens would be higher. Methods: We performed an aggregate data meta-analysis on nine studies to examine the incidence of ventricular arrhythmias. We further assessed a meta-regression analysis to evaluate the effect of duration of therapy on incidence of ventricular arrhythmias. Relative risk (RR) and 95% confidence intervals (CI) were estimated using a random-effects model. Results: Of 3809 patients being treated with ibrutinib, the incidence of ventricular arrhythmias was almost 8-fold higher in patients being treated with ibrutinib compared to other tyrosine kinase inhibitors (TKIs), other chemotherapies, or immunotherapy. (RR 8.13, 95% CI 4.37-15.10, p <0.0001). On meta-regression analysis, the incidence increased further with longer duration of treatment (coefficient = 0.0206, p=0.049); patient populations greater than 60 years have a higher incidence of ventricular arrhythmias (coefficient = 0.0237, p=0.044). Over 50% of patients diagnosed with ventricular arrhythmias on ibrutinib died of sudden death. Conclusions: For patients treated with ibrutinib, there was a markedly higher rate of ventricular arrhythmias and an increased incidence with longer duration of treatment. These data highlight the need for guidelines on surveillance and management for ventricular arrhythmias for patients taking ibrutinib.