Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib.
Academic Article
Overview
abstract
First-generation Bruton tyrosine kinase (BTK) inhibitor ibrutinib has been associated with an increased risk for cardiovascular toxicities. Zanubrutinib is a more selective, next-generation BTK inhibitor. In this manuscript, incidence rates of atrial fibrillation, symptomatic (grade ≥2) ventricular arrhythmia, and hypertension were evaluated in a pooled analysis of 10 clinical studies with zanubrutinib monotherapy in patients (N=1550) with B-cell malignancies and a pooled analysis of head-to-head studies comparing zanubrutinib with ibrutinib (ASPEN cohort 1; ALPINE). Across the 10 studies, most patients (median age, 67 years) were male (66.3%), and most had CLL/SLL (60.5%). Overall incidence and exposure-adjusted incidence rates (EAIR) for atrial fibrillation, symptomatic ventricular arrhythmia, and hypertension were lower with zanubrutinib versus ibrutinib. Despite a similar prevalence of pre-existing cardiovascular events in ASPEN and ALPINE, atrial fibrillation/flutter incidence rate (6.1% vs 15.6%) and EAIR (0.2 vs 0.64 persons/100 person-months; P<.0001) were lower with zanubrutinib than with ibrutinib, respectively. Symptomatic ventricular arrhythmia incidence was low for both zanubrutinib (0.7%) and ibrutinib (1.7%) with numerically lower EAIR (0.02 vs 0.06 persons/100 person-months, respectively) for zanubrutinib. The hypertension EAIR was lower with zanubrutinib versus ibrutinib in ASPEN but similar between treatment arms in ALPINE. The higher hypertension EAIR in ALPINE was inconsistent with the other zanubrutinib studies. However, fewer discontinuations (1 vs 14) and deaths (0 vs 6) due to cardiac disorders occurred with zanubrutinib versus ibrutinib in ALPINE. These data support zanubrutinib as a treatment option with improved cardiovascular tolerability over ibrutinib for patients with B-cell malignancies in need of BTK inhibitors. CT# NCT03053440 NCT03336333 NCT03734016 NCT04170283 NCT03206918 NCT03206970 NCT03332173 NCT03846427 NCT02343120 NCT03189524.
