{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:51:57Z","timestamp":1790635917640,"version":"4.1.0"},"reference-count":15,"publisher":"American Society of Hematology","issue":"20","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,11,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Acalabrutinib, a next-generation Bruton\u2019s 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\u00a0sudden-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\u2013BTKi-treated subjects (relative risk, 8.2; P\u00a0&amp;lt;\u00a0.001; 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.<\/jats:p>","DOI":"10.1182\/blood.2022016953","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T19:09:40Z","timestamp":1659467380000},"page":"2142-2145","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":65,"title":["Ventricular arrhythmias and sudden death events following acalabrutinib initiation"],"prefix":"10.1182","volume":"140","author":[{"given":"Seema A.","family":"Bhat","sequence":"first","affiliation":[{"name":"1Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9797-5979","authenticated-orcid":false,"given":"John","family":"Gambril","sequence":"additional","affiliation":[{"name":"2Division of Cardiology, Cardio-Oncology Program, The Ohio State University Medical Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leylah","family":"Azali","sequence":"additional","affiliation":[{"name":"3Department of Pharmacy, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6914-510X","authenticated-orcid":false,"given":"Sunnia T.","family":"Chen","sequence":"additional","affiliation":[{"name":"2Division of Cardiology, Cardio-Oncology Program, The Ohio State University Medical Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Rosen","sequence":"additional","affiliation":[{"name":"3Department of Pharmacy, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilly","family":"Palettas","sequence":"additional","affiliation":[{"name":"4Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy E.","family":"Wiczer","sequence":"additional","affiliation":[{"name":"3Department of Pharmacy, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4910-3433","authenticated-orcid":false,"given":"Sujay","family":"Kalathoor","sequence":"additional","affiliation":[{"name":"2Division of Cardiology, Cardio-Oncology Program, The Ohio State University Medical Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhong","family":"Zhao","sequence":"additional","affiliation":[{"name":"1Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5748-7874","authenticated-orcid":false,"given":"Kerry A.","family":"Rogers","sequence":"additional","affiliation":[{"name":"1Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Kittai","sequence":"additional","affiliation":[{"name":"1Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Grever","sequence":"additional","affiliation":[{"name":"1Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1813-9812","authenticated-orcid":false,"given":"Farrukh","family":"Awan","sequence":"additional","affiliation":[{"name":"5Division of Hematology, University of Texas - Southwestern, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Ruz","sequence":"additional","affiliation":[{"name":"2Division of Cardiology, Cardio-Oncology Program, The Ohio State University Medical Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Byrd","sequence":"additional","affiliation":[{"name":"6Department of Medicine, University of Cincinnati, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Woyach","sequence":"additional","affiliation":[{"name":"1Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9113-8333","authenticated-orcid":false,"given":"Daniel","family":"Addison","sequence":"additional","affiliation":[{"name":"2Division of Cardiology, Cardio-Oncology Program, The Ohio State University Medical Center, Columbus, OH"},{"name":"7Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"4","key":"2022111716253785800_bib1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1056\/NEJMoa1509981","article-title":"Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia","volume":"374","author":"Byrd","year":"2016","journal-title":"N\u00a0Engl J Med"},{"issue":"10121","key":"2022111716253785800_bib2","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0140-6736(17)33108-2","article-title":"Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial","volume":"391","author":"Wang","year":"2018","journal-title":"Lancet"},{"issue":"10232","key":"2022111716253785800_bib3","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/S0140-6736(20)30262-2","article-title":"Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial","volume":"395","author":"Sharman","year":"2020","journal-title":"Lancet"},{"issue":"24","key":"2022111716253785800_bib4","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1182\/blood.2020009617","article-title":"Acalabrutinib in treatment-naive chronic lymphocytic leukemia","volume":"137","author":"Byrd","year":"2021","journal-title":"Blood"},{"issue":"3","key":"2022111716253785800_bib5","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1158\/2159-8290.CD-19-1130","article-title":"Acalabrutinib plus obinutuzumab in treatment-na\u00efve and relapsed\/refractory chronic lymphocytic leukemia","volume":"10","author":"Woyach","year":"2020","journal-title":"Cancer Discov"},{"issue":"11","key":"2022111716253785800_bib6","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1158\/1078-0432.CCR-16-0463","article-title":"The bruton tyrosine kinase (BTK) inhibitor acalabrutinib demonstrates potent on-target effects and efficacy in two mouse\u00a0models of chronic lymphocytic leukemia","volume":"23","author":"Herman","year":"2017","journal-title":"Clin Cancer Res"},{"issue":"31","key":"2022111716253785800_bib7","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1200\/JCO.21.01210","article-title":"Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial","volume":"39","author":"Byrd","year":"2021","journal-title":"J\u00a0Clin Oncol"},{"issue":"suppl 1","key":"2022111716253785800_bib8","first-page":"S4","article-title":"Tyrosine kinase inhibitor associated polymorphic ventricular tachycardia","volume":"4","author":"Fazal","year":"2022","journal-title":"J\u00a0Am Coll Cardiol CardioOnc"},{"issue":"6","key":"2022111716253785800_bib9","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.jacc.2018.06.002","article-title":"Ventricular arrhythmias following ibrutinib initiation for lymphoid malignancies","volume":"72","author":"Guha","year":"2018","journal-title":"J\u00a0Am Coll Cardiol"},{"issue":"18","key":"2022111716253785800_bib10","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1182\/blood-2016-10-742437","article-title":"Ventricular\u00a0arrhythmias and sudden death in patients taking ibrutinib","volume":"129","author":"Lampson","year":"2017","journal-title":"Blood"},{"issue":"2","key":"2022111716253785800_bib11","doi-asserted-by":"crossref","first-page":"e004662","DOI":"10.1161\/CIRCEP.116.004662","article-title":"Incidence of idiopathic ventricular arrhythmias: a population-based study","volume":"10","author":"Sirichand","year":"2017","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2022111716253785800_bib12","unstructured":"National Cancer Institute\n          . 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