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Patients aged \u226565 years (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009269) were randomized 1:1 to once-daily ibrutinib 420\u2009mg continuously or chlorambucil 0.5\u20130.8\u2009mg\/kg for \u226412 cycles. With a median (range) follow-up of 60 months (0.1\u201366), progression-free survival (PFS) and overall survival (OS) benefits for ibrutinib versus chlorambucil were sustained (PFS estimates at 5 years: 70% vs 12%; HR [95% CI]: 0.146 [0.098\u20130.218]; OS estimates at 5 years: 83% vs 68%; HR [95% CI]: 0.450 [0.266\u20130.761]). Ibrutinib benefit was also consistent in patients with high prognostic risk (\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation, 11q deletion, and\/or unmutated IGHV\n                    <jats:italic>)<\/jats:italic>\n                    (PFS: HR [95% CI]: 0.083 [0.047\u20130.145]; OS: HR [95% CI]: 0.366 [0.181\u20130.736]). Investigator-assessed overall response rate was 92% with ibrutinib (complete response, 30%; 11% at primary analysis). Common grade \u22653 adverse events (AEs) included neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), and hyponatremia (6%); occurrence of most events as well as discontinuations due to AEs decreased over time. Fifty-eight percent of patients continue to receive ibrutinib. Single-agent ibrutinib demonstrated sustained PFS and OS benefit versus chlorambucil and increased depth of response over time.\n                  <\/jats:p>","DOI":"10.1038\/s41375-019-0602-x","type":"journal-article","created":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T08:05:56Z","timestamp":1571385956000},"page":"787-798","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":423,"title":["Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL\/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study"],"prefix":"10.1038","volume":"34","author":[{"given":"Jan A.","family":"Burger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Barr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadeusz","family":"Robak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Owen","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":"Alessandra","family":"Tedeschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osnat","family":"Bairey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hillmen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Coutre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Devereux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Grosicki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz","family":"Offner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indu","family":"Lal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Dean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Kipps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,18]]},"reference":[{"key":"602_CR1","unstructured":"National Cancer Institute. 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PMB reported a consultancy\/advisory role for AbbVie and Pharmacyclics LLC, an AbbVie Company; and research funding from Pharmacyclics LLC, an AbbVie Company. TR reported research funding from Pharmacyclics LLC, an AbbVie company. CO reported honoraria from Gilead, Janssen, AbbVie, Roche, Merck, Teva, and AstraZeneca. PG reported honoraria from AbbVie, Acerta, BeiGene, Gilead, Roche, Sunesis, Celgene, and Janssen; a consultancy\/advisory role from AbbVie, Acerta, BeiGene, Gilead, Janssen, Pharmacyclics LLC, an AbbVie Company, Celgene, and Sunesis; speakers\u2019 bureau for Gilead; and research funding from AbbVie, Gilead, Janssen, and Novartis. AT reported a consultancy\/advisory role for Janssen spa, Gilead, Sunesis, and AbbVie; and speakers\u2019 bureau for Janssen. OB reported a consultancy\/advisory role for AbbVie and research funding from Janssen. PH reported honoraria, a consultancy\/advisory role, and research funding from Janssen, Pharmacyclics LLC, an AbbVie Company, and AbbVie; and travel expenses from Janssen and AbbVie. SEC reported honoraria from Pharmacyclics LLC, an AbbVie Company, and Janssen; a consultancy\/advisory role for AbbVie, Astellas, AstraZeneca, Celgene, Genentech, Pharmacyclics LLC, an AbbVie Company, Novartis, and Janssen; travel, accommodations, expenses from AbbVie, BeiGene, Celgene, Genentech, Janssen, Pharmacyclics LLC, an AbbVie Company; expert testimony for Genentech; other relationship with BeiGene; and research funding from Celgene, Gilead, Janssen, Pharmacyclics LLC, an AbbVie Company, AbbVie, Takeda, and Acerta. SD reported a consultancy\/advisory role for AbbVie, Janssen, GlaxoSmithKline, and Bristol-Myers Squibb; and speakers\u2019 bureau and travel expenses for Janssen and Gilead. HM reported honoraria and travel expenses from AbbVie, Janssen, Novartis, and Roche; and a consultancy\/advisory role with Janssen. DS reported honoraria from Celgene, Roche, MSD, and Janssen; travel expenses from Celgene, Bristol-Myers Squibb, Janssen, and Novartis; and research funding from Amgen, MSD, Pharmacyclics LLC, an AbbVie Company, AbbVie, Sanofi, Roche, BeiGene, and Acerta. CM reported a consulting\/advisory role with Pharmacyclics LLC, an AbbVie Company, Janssen, and AbbVie. SD reported employment with Pharmacyclics LLC, an AbbVie Company; and stock ownership with AbbVie, Celgene, Gilead, GSK, and Exelixis. IL reported employment with Pharmacyclics, an AbbVie Company, and spouse employment with The Permanente Medical Group; and stock ownership with AbbVie, Gilead Sciences, Clovis, Infinity, The Permanente Medical Group, and Reviva Pharmaceuticals. JPD reported employment with Pharmacyclics LLC, an AbbVie Company, and CTI BioPharma Corp; and stock ownership with AbbVie and CTI BioPharma Corp. TJK reported a consultancy\/advisory role for AbbVie, Genentech-Roche, Gilead, Pharmacyclics LLC, an AbbVie Company, and Celgene; and research funding from AbbVie, Genentech-Roche, Pharmacyclics LLC, an AbbVie Company, and Oncternal. SG and FO reported no relevant financial disclosures.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}