Electrocardiographic Changes Associated With Ibrutinib Exposure

Abstract

Although ibrutinib-associated atrial and ventricular arrhythmias have been well described, there is little information about ibrutinib’s effects on other electrocardiographic parameters, particularly the QT interval. Using our database of 137 patients treated with ibrutinib, we retrospectively identified 21 patients in whom an electrocardiogram (ECG) was obtained both prior to and after ibrutinib exposure. All traditional ECG parameters as well as QT dispersion were manually measured by an electrophysiologist. Compared to baseline ECGs, post ibrutinib ECGs demonstrated QT interval shortening from 386 ms to 356 ms ( P = .007), corrected QT interval shortening using Bazett’s formula from 446 ms to 437 ms ( P = .04), and corrected QT interval shortening using Fridericia’s formula from 425 ms to 407 ms ( P = .003). QT dispersion also increased post ibrutinib exposure compared to baseline (39.8 ms vs 57.3 ms, P = .002). There was no significant change in other ECG parameters. In conclusion, both the absolute and corrected QT intervals significantly shortened after ibrutinib exposure, while there was a significant increase in QT dispersion. These findings may point to a common underlying electrophysiologic mechanism of ibrutinib-associated arrhythmias.

Ibrutinib-Associated Cardiotoxicity: From the Pharmaceutical to the Clinical

“… 26 However, in another study, Fradley et al retrospectively analyzed 137 patients and found that the incidence of short QT intervals tended to increase after ibrutinib exposure. 59 Furthermore, a sequential administration of single doses of therapeutic and super-therapeutic concentrations of ibrutinib revealed that ibrutinib shortened the QTc interval and prolonged the PR interval, which was consistent to the results from the Phase 1b/2 study 1102. 72 In conclusion, QT interval change is not strongly correlated with ibrutinib-induced cardiotoxicity.…”

“…A retrospective study that quantified the incidence rates and risk of AA in 137 patients treated with ibrutinib and in 106 patients diagnosed with B cell malignancies and treated with chemotherapy confirmed that the use of ibrutinib is an independent risk factor for the incidence of AA. 59 Ibrutinib use was also associated with a 5.2-fold increased risk of AA development, 14% in the ibrutinib-treated group versus 3% in the chemotherapy group.…”

Recognition, Prevention, and Management of Arrhythmias and Autonomic Disorders in Cardio-Oncology: A Scientific Statement From the American Heart Association

“…23,58 In fact, ibrutinib may shorten the QT interval, with enhanced automaticity and triggered activity suggested as mechanisms for arrhythmogenesis. 24,25,59,60…”

Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies

“…Fradley et al enrolled 137 patients who were treated with ibrutinib, 21 pre-and post-ibrutinib ECG readings were obtained. Compared with the pre ibrutinib ECG, after administration, the ECG showed QT interval shortening from 446 to 437 ms, based on Bazett's formula (47). In another phase II clinical trial, a mean 7.5 ms shortening of the corrected QT interval was found after ibrutinib treatment (34).…”