The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site. The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. My Bibliography Citation manager Save citation to file Add to Collections Add to My Bibliography Your saved search Create a file for external citation management software First-generation Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been associated with an increased risk of cardiovascular toxicities. Zanubrutinib is a more selective, next-generation BTK inhibitor. In this analysis, incidence rates of atrial fibrillation, symptomatic (grade ≥2) ventricular arrhythmia, and hypertension were evaluated in a pooled analysis of 10 clinical studies with zanubrutinib monotherapy in patients (N = 1550) with B-cell malignancies and a pooled analysis of head-to-head studies comparing zanubrutinib with ibrutinib (ASPEN cohort 1; ALPINE). Among the 10 studies, most patients (median age, 67 years) were male (66.3%) and had CLL/SLL (60.5%). Overall incidence and exposure-adjusted incidence rates (EAIR) for atrial fibrillation, symptomatic ventricular arrhythmia, and hypertension were lower with zanubrutinib than ibrutinib. Despite a similar prevalence of preexisting cardiovascular events in ASPEN and ALPINE, atrial fibrillation/flutter incidence rates (6.1% vs 15.6%) and EAIR (0.2 vs 0.64 persons per 100 person-months; P < .0001) were lower with zanubrutinib than with ibrutinib. Symptomatic ventricular arrhythmia incidence was low for both zanubrutinib (0.7%) and ibrutinib (1.7%) with numerically lower EAIR (0.02 vs 0.06 persons per 100 person-months, respectively) for zanubrutinib. The hypertension EAIR was lower with zanubrutinib than ibrutinib in ASPEN but similar between treatment arms in ALPINE. The higher hypertension EAIR in ALPINE was inconsistent with other zanubrutinib studies. However, fewer discontinuations (1 vs 14) and deaths (0 vs 6) due to cardiac disorders occurred with zanubrutinib versus ibrutinib in ALPINE. These data support zanubrutinib as a treatment option with improved cardiovascular tolerability compared with ibrutinib for patients with B-cell malignancies in need of BTK inhibitors. These trials were registered at www.ClinicalTrials.gov as # NCT03053440 , NCT03336333 , NCT03734016 , NCT04170283 , NCT03206918 , NCT03206970 , NCT03332173 , NCT03846427 , NCT02343120 , and NCT03189524 . © 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. PubMed Disclaimer Conflict of interest statement Conflict-of-interest disclosure: J.J.M. reports financial support from Bristol Myers Squibb (BMS), Deciphera, Takeda, AstraZeneca, Regeneron, Janssen, Myovant, Silverback Therapeutics, Kurome Therapeutics, Kiniksa Pharmaceuticals, Daiichi Sankyo, CRC Oncology, BeiGene, Pharmacyclics, Prelude Therapeutics, TransThera Sciences, Antev Ltd, IQVIA, Incyte, AskBio, Labcorp, Paladin, Quell Therapeutics, Voyager Therapeutics, CRC Oncology, Bitterroot Bio, Repare Therapeutics, Teva, and Cytokinetics and is supported by grants from the National Institutes of Health (grants R01HL141466, R01HL155990, R01HL156021, and R01HL160688). R.R.F. reports a consulting or advisory role with AbbVie, AstraZeneca, BeiGene, Genentech, Janssen, Lilly Oncology, Sanofi, MEI Pharma, and X4 Pharmaceuticals; and reports speaker fees from AstraZeneca and Janssen. C.S.T. reports honoraria from Janssen, AbbVie, BeiGene, Loxo Oncology, Novartis; research funding from Janssen, AbbVie, BeiGene. J.E-S reports research funding from Novartis; consulting fees from CRC Oncology, Repare Therapeutics, and BMS; honoraria from Servier, Eiasi, BeiGene, and IPSN; meeting support from BeiGene; and equipment, materials, or other services support from BMS. C.R.F. reports a consulting or advisory role with Bayer, Gilead, Spectrum, AbbVie, Celgene, Denovo Biopharma, BeiGene, Karyopharm Therapeutics, Pharmacyclics/Janssen, Genentech/Roche, Epizyme, Genmab, Seagen, Foresight Diagnostics, BMS/Celgene, Curio Science, AstraZeneca, and MorphoSys; and stock ownership with Foresight Diagnostics and NPower. A.C., H.M., M.Z., J.Z., and L.C. report employment and stock ownership with BeiGene. J.R.B. reports research funding from BeiGene, Gilead, iOnctura, Loxo/Lilly, MEI Pharma, Sun, Verastem Oncology/Secura Bio, and TG Therapeutics; consulting fees from AbbVie, Acerta/AstraZeneca, BeiGene, BMS/Juno/Celgene, Catapult, Eli Lilly, Genentech/Roche, Grifols Worldwide Operations, HUTCHMED, iOnctura, Janssen, Loxo, MEI Pharma, MorphoSys AG, Nextcea, Novartis, Pfizer, Pharmacyclics, and Rigel; and served on data safety monitoring Committees for Invectys. Graphical abstract Graphical abstract Cardiovascular toxicity of Bruton tyrosine kinase inhibitors: forget about selectivity but watch the clock. Minotti G. Minotti G. Blood Adv. 2024 Jul 23;8(14):3810-3812. doi: 10.1182/bloodadvances.2024013348. Blood Adv. 2024. PMID: 38696711 Free PMC article. No abstract available. Gayko U, Fung M, Clow F, et al. Development of the Bruton's tyrosine kinase inhibitor ibrutinib for B cell malignancies. Ann N Y Acad Sci. 2015;1358:82–94. - PubMed Gayko U, Fung M, Clow F, et al. Development of the Bruton's tyrosine kinase inhibitor ibrutinib for B cell malignancies. Ann N Y Acad Sci. 2015;1358:82–94. - PubMed O'Brien S, Jones JA, Coutre SE, et al. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicenter study. Lancet Oncol. 2016;17(10):1409–1418. - PubMed O'Brien S, Jones JA, Coutre SE, et al. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicenter study. Lancet Oncol. 2016;17(10):1409–1418. - PubMed Dimopoulos MA, Tedeschi A, Trotman J, et al. Phase 3 trial of ibrutinib plus rituximab in Waldenstrom's macroglobulinemia. N Engl J Med. 2018;378(25):2399–2410. - PubMed Dimopoulos MA, Tedeschi A, Trotman J, et al. Phase 3 trial of ibrutinib plus rituximab in Waldenstrom's macroglobulinemia. N Engl J Med. 2018;378(25):2399–2410. - PubMed Wang ML, Lee H, Chuang H, et al. Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-center, open-label, phase 2 trial. Lancet Oncol. 2016;17(1):48–56. - PubMed Wang ML, Lee H, Chuang H, et al. Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-center, open-label, phase 2 trial. Lancet Oncol. 2016;17(1):48–56. - PubMed Lampson BL, Yu L, Glynn RJ, et al. Ventricular arrhythmias and sudden death in patients taking ibrutinib. Blood. 2017;129(18):2581–2584. - PMC - PubMed Lampson BL, Yu L, Glynn RJ, et al. Ventricular arrhythmias and sudden death in patients taking ibrutinib. 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