Next-generation Bruton’s tyrosine kinase inhibitor (BTKi) acalabrutinib has a strikingly effective anti-B-cell cancer activity. Unknown ventricular arrhythmias (VAs) associated with next-generation BTKi treatment have recently been documented. However, it was uncertain if acalabrutinib correlated with VAs in long-term follow-up. For a study, researchers evaluated the prevalence of VAs using data from a large cohort of 290 B-cell malignancies patients who received acalabrutinib treatment continuously between 2014 and 2020. 

Incident VA development was the main endpoint (ventricular fibrillation, ventricular tachycardia, and symptomatic premature ventricular contractions). To establish the possibility of an acalabrutinib relationship, probability scores were calculated. The incident rates were determined as a function of the length of therapy. Utilizing relative-risks, weighted average observed incidence rates were contrasted with anticipated population rates. For acalabrutinib-associated VAs, the absolute excess risk (AER) was calculated. 

With a median time to event of 14.9 months, there were 8 incident-VA cases over 1,063 person-years of follow-up, including 6 in individuals without coronary disease (CAD) or heart failure (HF) and 1 sudden death. The weighted average incidence among individuals without a history of ibrutinib usage, CAD, or HF was 394 per 100,000 person-years, compared to a reported incidence of 48.1 among participants of a similar age not receiving BTK inhibitor treatment (relative risk, 8.2; P< .001; AER, 346). 

No cardiac or electrocardiographic factors were connected to the development of VA other than age. Therefore, the results are taken together, implied that VAs could be a class effect of BTKi treatments.

Reference: ashpublications.org/blood/article-abstract/140/20/2142/486090/Ventricular-arrhythmias-and-sudden-death-events?redirectedFrom=fulltext