{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:01:00Z","timestamp":1791406860643,"version":"4.3.3"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Takeda Development Center Americas, Inc."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The primary analysis of the phase 2 OPTIC trial (NCT02467270) demonstrated optimal benefit:risk with response-based ponatinib dosing (45\u2009mg once daily (QD) reduced to 15\u2009mg QD) upon achieving \u22641%\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    <jats:sup>IS<\/jats:sup>\n                    in patients with tyrosine kinase inhibitor-resistant or T315I-positive chronic-phase chronic myeloid leukemia (CP-CML). Here, we report 5-year long-term outcomes. Overall, 283 patients were randomized to 45-mg, 30-mg, or 15-mg QD starting doses (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200994, 95, and 94, respectively), with dose reduction to 15\u2009mg QD upon response in the 45-mg and 30-mg cohorts. At data cutoff, 61 patients remained on trial. Median follow-up time was 75\u201378 months. By 5 years, 60%, 41%, and 40% of patients in the 45-mg, 30-mg, and 15-mg cohorts, respectively, achieved \u22641%\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    <jats:sup>IS<\/jats:sup>\n                    . Five-year progression-free survival rates were 63%, 57%, and 60%, respectively, by cohort; overall survival rates exceeded 80%. In patients with a T315I mutation, 5-year rates of \u22641%\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    <jats:sup>IS<\/jats:sup>\n                    , PFS, and OS were highest in the 45-mg cohort. Exposure-adjusted rates of adjudicated arterial occlusive events were 4.1, 3.8, and 2.0 patients per 100 patient-years, respectively, by cohort; results were comparable in T315I-positive patients. These findings support long-term clinical benefit of response-based ponatinib dosing in third-line CP-CML, especially in patients with the T315I mutation.\n                  <\/jats:p>","DOI":"10.1038\/s41375-026-03009-x","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:03:30Z","timestamp":1784898210000},"page":"1882-1892","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Five-year follow-up of OPTIC: long-term efficacy, safety, and mutation analyses of ponatinib in chronic-phase chronic myeloid leukemia from a randomized phase 2 trial"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-3307","authenticated-orcid":false,"given":"Hagop","family":"Kantarjian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-1331","authenticated-orcid":false,"given":"Michael","family":"Deininger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1710-1794","authenticated-orcid":false,"given":"Jane F.","family":"Apperley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9147-9090","authenticated-orcid":false,"given":"Christopher Kevin","family":"Arthur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Chuah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0626-0834","authenticated-orcid":false,"given":"Andreas","family":"Hochhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4988-2564","authenticated-orcid":false,"given":"Hugues","family":"de Lavallade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7391-7168","authenticated-orcid":false,"given":"Jeffrey H.","family":"Lipton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3290-7961","authenticated-orcid":false,"given":"Elza","family":"Lomaia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"McCloskey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Maness","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2251-4032","authenticated-orcid":false,"given":"Michael","family":"Mauro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Moiraghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Pavlovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianantonio","family":"Rosti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Rousselot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Vorog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Evan","family":"Reddick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niti","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meliessa","family":"Hennessy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammie","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-1071","authenticated-orcid":false,"given":"Jorge","family":"Cortes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"3009_CR1","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1200\/JCO.2015.66.2866","volume":"34","author":"H Bower","year":"2016","unstructured":"Bower H, Bj\u00f6rkholm M, Dickman PW, H\u00f6glund M, Lambert PC, Andersson TM. 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Iclusig [package insert]. Lexington, MA: Takeda Pharmaceuticals America, Inc.; 2025."}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41375-026-03009-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-026-03009-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-026-03009-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:02:20Z","timestamp":1790103740000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41375-026-03009-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":29,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["3009"],"URL":"https:\/\/doi.org\/10.1038\/s41375-026-03009-x","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]},"assertion":[{"value":"30 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 June 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 July 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2026","order":6,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":7,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The license has been updated to CC BY.","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"HK: Research grants and honoraria: Amgen, Ascentage, Novartis, Pfizer; honoraria: Amgen, Stemline. MD: Advisory board participation: Ascentage, Pfizer, Novartis, Takeda. JFA: Research support: Pfizer, Incyte; advisory board participation: Novartis, Incyte; honoraria as speaker: Novartis, Incyte, Paladin. CKA: Nothing to disclose. CC: Honoraria: Korea Otsuka Pharmaceutical; honoraria and research funding: Bristol Myers Squibb, Novartis; travel and research funding: Pfizer. AH: Research funding: Bristol Myers Squibb, Novartis, Pfizer, Incyte, Enliven, Terns Pharma. HdL: Honoraria and research funding: Bristol Myers Squibb, Incyte; honoraria: Pfizer, Novartis. JHL: Consultancy and research funding: Bristol Myers Squibb, Takeda, Pfizer, Novartis. EL: Speakers bureau: Novartis, Pfizer, Fusion Pharma; travel, accommodation, and expenses: Novartis, Pfizer. JM: Nothing to disclose. LM: Nothing to disclose. MM: Consultancy, honoraria, travel, accommodation, expenses, and research funding: Bristol Myers Squibb, Novartis, Takeda, Pfizer; research funding: Sun Pharma\/SPARC. BM: Speakers Bureau: Novartis, Pfizer, Takeda. CP: Speakers bureau: Novartis, Pfizer, Pint Pharma, Ascentage, BeOne; advisory board participation: Novartis, Ascentage. GR: Research funding and speakers bureau: Pfizer; speakers bureau: Bristol Myers Squibb, Incyte, Novartis. PR: Nothing to disclose. BC: Employment: Takeda Development Center Americas, Inc. AV: Employment: Takeda Development Center Americas, Inc. LER: Employment: Takeda Development Center Americas, Inc. NP: Employment: Takeda Development Center Americas, Inc. MH: Employment: Takeda Development Center Americas, Inc. TY: Employment: Takeda Development Center Americas, Inc. JC: Grant or research support (to institution): Novartis, Sun Pharma, Ascentage, Terns Pharma, Cyto Agents, Kura Oncology; paid consultant: Novartis, Pfizer, Sun Pharma, Takeda, Tern Pharma, Incyte, Ascentage, Enliven, Syndax, Jenssen, Xspray.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}