Analysis of ventricular arrhythmias and sudden death from prospective, randomized clinical trials of acalabrutinib

Jeff P Sharman; Paolo Ghia; Paulo Miranda; Naghmana Bajwa; Simon Rule; Bob Shaw; John F Seymour

doi:10.1111/bjh.19469

Analysis of ventricular arrhythmias and sudden death from prospective, randomized clinical trials of acalabrutinib

Br J Haematol. 2024 Apr 17. doi: 10.1111/bjh.19469. Online ahead of print.

Authors

Jeff P Sharman¹, Paolo Ghia^{2

3}, Paulo Miranda⁴, Naghmana Bajwa⁵, Simon Rule⁶, Bob Shaw⁶, John F Seymour⁷

Affiliations

¹ Willamette Valley Cancer Institute and Research Center/US Oncology Research, Eugene, Oregon, USA.
² Università Vita-Salute San Raffaele, Milano, Italy.
³ IRCCS Ospedale San Raffaele, Milano, Italy.
⁴ AstraZeneca, Gaithersburg, Maryland, USA.
⁵ AstraZeneca, Wilmington, Delaware, USA.
⁶ AstraZeneca, Cambridge, UK.
⁷ Peter MacCallum Cancer Centre, Royal Melbourne Hospital and University of Melbourne, Melbourne, Victoria, Australia.

PMID: 38634256
DOI: 10.1111/bjh.19469

Abstract

This analysis investigated the incidence of sudden deaths (SDs) and non-fatal and fatal ventricular arrhythmias (VAs) in five acalabrutinib clinical trials. In total, 1299 patients received acalabrutinib (exposure, 4568.4 patient-years). Sixteen (1.2%) patients experienced SD or VA (event rate, 0.350/100 patient-years). Non-fatal VAs occurred in 11 (0.8%) patients, nine (0.7%) of whom had premature ventricular contractions only. SD and fatal VAs occurred in five (0.4%) patients (event rate, 0.109/100 patient-years; median time to event: 46.2 months). SDs and VAs with acalabrutinib occurred at low rates, and there are insufficient data to point to an increased risk of SD or VA with acalabrutinib.

Keywords: acalabrutinib; ibrutinib; sudden cardiac death; sudden death; ventricular arrhythmia.

Grants and funding

AstraZeneca