{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:59:14Z","timestamp":1793386754811,"version":"4.5.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Acerta Pharma, a member of the AstraZeneca group","id":[{"id":"https:\/\/ror.org\/01cdq6t90","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2022,4]]},"DOI":"10.1038\/s41375-021-01485-x","type":"journal-article","created":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T01:41:52Z","timestamp":1641001312000},"page":"1171-1175","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":200,"title":["Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-na\u00efve chronic lymphocytic leukemia"],"prefix":"10.1038","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-6115","authenticated-orcid":false,"given":"Jeff P.","family":"Sharman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miklos","family":"Egyed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-8084","authenticated-orcid":false,"given":"Wojciech","family":"Jurczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Skarbnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5745-8125","authenticated-orcid":false,"given":"John M.","family":"Pagel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6724-290X","authenticated-orcid":false,"given":"Ian W.","family":"Flinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manali","family":"Kamdar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talha","family":"Munir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Walewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Corbett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Maria","family":"Fogliatto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Herishanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Versha","family":"Banerji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8420-5748","authenticated-orcid":false,"given":"Steven","family":"Coutre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Follows","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Karlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3750-7342","authenticated-orcid":false,"given":"Paolo","family":"Ghia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Janssens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Cymbalista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3403-9144","authenticated-orcid":false,"given":"Jennifer A.","family":"Woyach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Ferrant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7357-270X","authenticated-orcid":false,"given":"William G.","family":"Wierda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerendra","family":"Munugalavadla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Hui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Byrd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,1]]},"reference":[{"key":"1485_CR1","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41375-020-01072-6","volume":"35","author":"T Wen","year":"2021","unstructured":"Wen T, Wang J, Shi Y, Qian H, Liu P. Inhibitors targeting Bruton\u2019s tyrosine kinase in cancers: drug development advances. Leukemia. 2021;35:312\u201332.","journal-title":"Leukemia"},{"key":"1485_CR2","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1056\/NEJMoa1812836","volume":"379","author":"JA Woyach","year":"2018","unstructured":"Woyach JA, Ruppert AS, Heerema NA, Zhao W, Booth AM, Ding W, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379:2517\u201328.","journal-title":"N Engl J Med"},{"key":"1485_CR3","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1056\/NEJMoa1817073","volume":"381","author":"TD Shanafelt","year":"2019","unstructured":"Shanafelt TD, Wang XV, Kay NE, Hanson CA, O\u2019Brien S, Barrientos J, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381:432\u201343.","journal-title":"N Engl J Med"},{"key":"1485_CR4","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S1470-2045(18)30788-5","volume":"20","author":"C Moreno","year":"2019","unstructured":"Moreno C, Greil R, Demirkan F, Tedeschi A, Anz B, Larratt L, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20:43\u201356.","journal-title":"Lancet Oncol"},{"key":"1485_CR5","doi-asserted-by":"publisher","first-page":"103238","DOI":"10.1016\/j.critrevonc.2021.103238","volume":"159","author":"L Pellegrini","year":"2021","unstructured":"Pellegrini L, Novak U, Andres M, Suter T, Nagler M. Risk of bleeding complications and atrial fibrillation associated with ibrutinib treatment: a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2021;159:103238.","journal-title":"Crit Rev Oncol Hematol"},{"key":"1485_CR6","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s00277-020-04094-3","volume":"100","author":"WJ Archibald","year":"2021","unstructured":"Archibald WJ, Rabe KG, Kabat BF, Herrmann J, Ding W, Kay NE, et al. Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib: risk prediction, management, and clinical outcomes. Ann Hematol. 2021;100:143\u201355.","journal-title":"Ann Hematol"},{"key":"1485_CR7","doi-asserted-by":"publisher","first-page":"3327","DOI":"10.1182\/blood.2020009617","volume":"137","author":"JC Byrd","year":"2021","unstructured":"Byrd JC, Woyach JA, Furman RR, Martin P, O\u2019Brien S, Brown JR, et al. Acalabrutinib in treatment-na\u00efve chronic lymphocytic leukemia. Blood. 2021;137:3327\u201338.","journal-title":"Blood"},{"key":"1485_CR8","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1158\/2159-8290.CD-19-1130","volume":"10","author":"JA Woyach","year":"2020","unstructured":"Woyach JA, Blachly JS, Rogers KA, Bhat SA, Jianfar M, Lozanski G, et al. Acalabrutinib plus obinutuzumab in treatment-naive and relapsed\/refractory chronic lymphocytic leukemia. Cancer Disco. 2020;10:394\u2013405.","journal-title":"Cancer Disco"},{"key":"1485_CR9","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1016\/S0140-6736(20)30262-2","volume":"395","author":"JP Sharman","year":"2020","unstructured":"Sharman JP, Egyed M, Jurczak W, Skarbnik A, Pagel JM, Kamdar M, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395:1278\u201391.","journal-title":"Lancet"},{"key":"1485_CR10","doi-asserted-by":"publisher","first-page":"e400","DOI":"10.3324\/haematol.2017.169334","volume":"102","author":"J Golay","year":"2017","unstructured":"Golay J, Ubiali G, Introna M. The specific Bruton tyrosine kinase inhibitor acalabrutinib (ACP-196) shows favorable in vitro activity against chronic lymphocytic leukemia B cells with CD20 antibodies. Haematologica. 2017;102:e400\u2013e403.","journal-title":"Haematologica"},{"issue":"Suppl 1","key":"1485_CR11","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1182\/blood-2020-139483","volume":"136","author":"CC Chu","year":"2020","unstructured":"Chu CC, Pinney JJ, Blick-Nitko SK, Baran AM, Peterson DR, Whitehead HE, et al. Ibrutinib off-target inhibition inhibits antibody-dependent cellular phagocytosis but not efferocytosis of CLL cells [abstract]. Blood. 2020;136 Suppl 1:45.","journal-title":"Blood"},{"key":"1485_CR12","doi-asserted-by":"publisher","first-page":"3441","DOI":"10.1200\/JCO.21.01210","volume":"39","author":"JC Byrd","year":"2021","unstructured":"Byrd JC, Hillmen P, Ghia P, Kater AP, Chanan-Khan A, Furman RR, et al. Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial. J Clin Oncol. 2021;39:3441\u201352.","journal-title":"J Clin Oncol"}],"updated-by":[{"DOI":"10.1038\/s41375-024-02487-1","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000}}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41375-021-01485-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-021-01485-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-021-01485-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T02:02:56Z","timestamp":1733277776000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41375-021-01485-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,1]]},"references-count":12,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["1485"],"URL":"https:\/\/doi.org\/10.1038\/s41375-021-01485-x","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,1]]},"assertion":[{"value":"19 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 November 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 January 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2022","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this article was revised: The wrong Supplementary file was originally published with this article; it has now been replaced with the correct file. The original article has been corrected.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2024","order":8,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":9,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":10,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41375-024-02487-1","URL":"https:\/\/doi.org\/10.1038\/s41375-024-02487-1","order":11,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"JS: Research funding from Seattle Genetics; research funding and consulting from AbbVie, AstraZeneca, BeiGene, BMS, Genentech, Gilead, Lilly, Pharmacyclics, TG Therapeutics; scientific board for Centessa; employment from US Oncology. ME: Nothing to disclose. WJ: Research funding from AstraZeneca, Janssen, and Loxo. AS: Consulting fees from AbbVie, AstraZeneca, Celgene, Genentech, GenMab, Kite, MorphoSys, Novartis, Pharmacyclics, Janssen, Alexion, Seattle Genetics, and TG Therapeutics; honoraria from AbbVie, AstraZeneca, BeiGene, Celgene, Genentech, Jazz Pharmaceuticals, Kite, Seattle Genetics, Pharmacyclics, Janssen, and TG Therapeutics; data safety monitoring board\/advisory board participation for Alexion. JP:\ufeff Consulting and speaker bureau for AstraZeneca. IF:\ufeff Consulting fees from AbbVie, AstraZeneca, BeiGene, Genentech, Gilead, Great Point Partners, Iksuda, Janssen, Juno, Kite, MorphoSys, Nurix, Pharmacyclics, Roche, Seattle Genetics, Takeda, TG Therapeutics, Unum, Verastem, and Yingli; grants from AbbVie, Acerta, Agios, ArQule, AstraZeneca, BeiGene, Calithera, Celgene, Constellation, Curis, Forma, Forty Seven, Genentech, Gilead, IGM Biosciences, Incyte, Infinity, Janssen, Juno, Karyopharm, Kite, Loxo, Merck, MorphoSys, Novartis, Pfizer, Pharmacyclics, Portola, Rhizen, Roche, Seattle Genetics, Takeda, Teva, TG Therapeutics, Trilium, Triphase, Unum, and Verastem. MK: Research support\/funding from TG Therapeutics\u00a0and Genentech; consulting for AbbVie, Karyopharm, Kite, AstraZeneca, Celgene\/Bristol Myers Squibb, Adaptive, and ADC Therapeutics; speaker\u2019s bureau for Seagen; data monitoring committee member for Celgene and Genentech. TM: Consulting\/advisory role for Morphosys, Sunesis, AstraZeneca, Janssen; honoraria from Janssen, AstraZeneca, Gilead, and Novartis. RW: Nothing to disclose. GC: Nothing to disclose. LMF: Nothing to disclose. YH: Honoraria from AbbVie, Janssen, AstraZeneca, and Roche. VB: Honoraria from AbbVie, Janssen, and AstraZeneca; grant funding from the Canadian Institutes of Health Research, Leukemia Lymphoma Society of Canada, CancerCare Manitoba Foundation, and the Hairy Cell Leukemia Foundation. SC: Honoraria from Janssen Oncology and Pharmacyclics; consulting for AbbVie, Adaptive Biotechnologies, AstraZeneca, BeiGene, Genentech\/Roche, Janssen Oncology, and Pharmacyclics; clinical research support from AbbVie, Acerta Pharma\/AstraZeneca, Janssen Oncology, Pharmacyclics; expert testimony for Genentech. GF: Consulting fees from AstraZeneca, Roche, AbbVie, Janssen, Karyopharm, Bristol Myers Squibb, and Centessa; honoraria from AstraZeneca, Roche, AbbVie, and Janssen; travel support from Roche, Janssen, and Bristol Myers Squibb. PW: Travel support from Roche; honoraria from AstraZeneca. KK: Nothing to disclose. PG: Honoraria from AbbVie, AstraZeneca, ArQule\/MSD, BeiGene, Janssen, Loxo\/Lilly, and Roche; research support from AbbVie, AstraZeneca, Janssen, and Sunesis. AJ: Consulting fees from Janssen, Roche, Gilead, AbbVie, Novartis, Amgen, Sanofi-Genzyme, and AstraZeneca; honoraria from Janssen, Roche, AbbVie, Novartis, Amgen, AstraZeneca, and BeiGene; travel support from AbbVie, Roche, Amgen, and Bristol Myers Squibb\/Celgene. FC: Consulting fees from AbbVie; honoraria from Roche, AbbVie, AstraZeneca, and Janssen; travel support from AstraZeneca, Roche, and AbbVie. JW: Consulting for AbbVie, Janssen, Pharmacyclics, BeiGene, AstraZeneca, ArQule, and Loxo; research support from Loxo and AbbVie; clinical trial support from Karyopharm, Morphosys, Pharmacyclics, and Janssen. EF: Honoraria from Janssen-Cilag; payment for expert testimony from Gilead, AbbVie, and Janssen-Cilag. WW: Grants\/contracts from GSK\/Novartis, AbbVie, Genentech, Pharmacyclics, AstraZeneca\/Acerta, Gilead, Juno, Kite, Sunesis, Miragen, Oncternal, Cyclacel, Loxo, Janssen, and Xencor. VM: Stock from and employment by AstraZeneca; family member association with Gilead. TY: Employment by AstraZeneca; stock from AstraZeneca, Johnson & Johnson, and AbbVie. MHW: Stock from and employment by AstraZeneca. JB: Stock and other ownership interests from Vincerx; honoraria from Pharmacyclics, AstraZeneca, Novartis, Syndax, and Trillium; consulting or advisory role for Acerta, Janssen, Kura, Novartis, Syndax, and AstraZeneca; research funding from Acerta, Pharmacyclics, and Zencor; patents, royalties, and other intellectual property from OSU Patents; travel support from Gilead, Janssen, Novartis, Pharmacyclics, and TG Therapeutics.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}