Ventricular arrhythmias and sudden death events following acalabrutinib initiation.

Autor:	Bhat SA; Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH., Gambril J; Division of Cardiology, Cardio-Oncology Program, The Ohio State University Medical Center, Columbus, OH., Azali L; Department of Pharmacy, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH., Chen ST; Division of Cardiology, Cardio-Oncology Program, The Ohio State University Medical Center, Columbus, OH., Rosen L; Department of Pharmacy, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH., Palettas M; Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University, Columbus, OH., Wiczer TE; Department of Pharmacy, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH., Kalathoor S; Division of Cardiology, Cardio-Oncology Program, The Ohio State University Medical Center, Columbus, OH., Zhao Q; Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH., Rogers KA; Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH., Kittai A; Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH., Grever M; Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH., Awan F; Division of Hematology, University of Texas - Southwestern, Dallas, TX., Ruz P; Division of Cardiology, Cardio-Oncology Program, The Ohio State University Medical Center, Columbus, OH., Byrd JC; Department of Medicine, University of Cincinnati, Cincinnati, OH., Woyach J; Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH., Addison D; Division of Cardiology, Cardio-Oncology Program, The Ohio State University Medical Center, Columbus, OH.; Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2022 Nov 17; Vol. 140 (20), pp. 2142-2145.
DOI:	10.1182/blood.2022016953
Abstrakt:	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. (© 2022 by The American Society of Hematology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu