Ventricular arrhythmias and sudden death events following acalabrutinib initiation

Seema A. Bhat, John Gambril, Leylah Azali, Sunnia T. Chen, Lindsay Rosen, Marilly Palettas, Tracy E. Wiczer, Sujay Kalathoor, Qiuhong Zhao, Kerry A. Rogers, Adam Kittai, Michael Grever, Farrukh Awan, Patrick Ruz, John C. Byrd, Jennifer Woyach, Daniel Addison

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Acalabrutinib, a next-generation Bruton's tyrosine kinase inhibitor (BTKi), associates with dramatic efficacy against B-cell malignancies. Recently, unexplained ventricular arrhythmias (VAs) with next-generation BTKi-therapy have been reported. Yet, whether acalabrutinib associates with VAs in long-term follow-up is unknown. Leveraging a large-cohort of 290 consecutive B-cell malignancy patients treated with acalabrutinib from 2014 to 2020, we assessed the incidence of VAs. The primary-endpoint was incident VA development (ventricular fibrillation, ventricular tachycardia, and symptomatic premature ventricular contractions). Probability-scores were assessed to determine likelihood of acalabrutinib-association. Incident rates as function of time-on-therapy were calculated. Weighted average observed incidence rates were compared with expected population rates using relative-risks. Absolute excess risk (AER) for acalabrutinib-associated VAs was estimated. Over 1063 person-years of follow-up, there were 8 cases of incident-VAs, including 6 in those without coronary disease (CAD) or heart failure (HF) and 1 sudden-death; median time-to-event 14.9 months. Among those without prior ibrutinib-use, CAD, or HF, the weighted average incidence was 394 per 100 000 person years compared with a reported incidence of 48.1 among similar-aged non–BTKi-treated subjects (relative risk, 8.2; P <. 001; AER, 346). Outside of age, no cardiac or electrocardiographic variables associated with VA development. Collectively, these data suggest VAs may be a class-effect of BTKi therapies.

Original languageEnglish (US)
Pages (from-to)2142-2145
Number of pages4
Issue number20
StatePublished - Nov 17 2022

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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