{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:23:30Z","timestamp":1792783410063,"version":"4.5.0"},"reference-count":5,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP 24K11508"],"award-info":[{"award-number":["JP 24K11508"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Akita University","id":[{"id":"https:\/\/ror.org\/03hv1ad10","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The arterial occlusive events (AOEs) associated with ponatinib are dose-dependent. Although the phase II OPTIC trial showed that reducing the dose to 15\u00a0mg daily (QD) after achieving a response provided an optimal benefit-risk profile, this has not been adequately verified using plasma drug concentrations data. A 66-year-old woman with chronic-phase chronic myeloid leukemia (CP-CML) was switched to ponatinib because of nilotinib-induced grade 3 thrombocytopenia. For safety, ponatinib was initiated at 15\u00a0mg every other day (Q2D) and gradually increased to 45\u00a0mg QD. A major molecular response (MMR) was achieved 30.6\u00a0months after starting ponatinib. The dose was then reduced to 15\u00a0mg QD to mitigate cardiovascular risks, and the MMR was successfully sustained for approximately 2\u00a0years (21.2\u00a0months) at this reduced dose. The total overall observation period was more than 5\u00a0years (65.2\u00a0months). A strong correlation was observed between the ponatinib dose and plasma trough concentrations (R\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.8132). Although 30\u00a0mg QD was required to reach the target concentration for suppressing resistant clones (23\u00a0ng\/mL), MMR was sustained at 15\u00a0mg QD, with a trough level of 14.1\u00a0ng\/mL. Once the tumor burden is significantly reduced, lower concentrations of ponatinib may be sufficient to maintain the molecular response.\n                  <\/jats:p>","DOI":"10.1007\/s12185-026-04254-7","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:41:05Z","timestamp":1784043665000},"page":"590-593","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Therapeutic drug monitoring guides personalized ponatinib dose reduction for chronic myeloid leukemia"],"prefix":"10.1007","volume":"124","author":[{"given":"Maiko","family":"Abumiya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6758-3787","authenticated-orcid":false,"given":"Naoto","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"4254_CR1","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1182\/blood.2021012082","volume":"138","author":"J Cortes","year":"2021","unstructured":"Cortes J, Apperley J, Lomaia E, Moiraghi B, Undurraga Sutton M, Pavlovsky C, et al. Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial. Blood. 2021;138:2042\u201350.","journal-title":"Blood"},{"key":"4254_CR2","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.leukres.2017.11.012","volume":"64","author":"M Abumiya","year":"2017","unstructured":"Abumiya M, Miura M, Takahashi N. Therapeutic drug monitoring of ponatinib using a simple high-performance liquid chromatography method in Japanese patients. Leuk Res. 2017;64:42\u20135.","journal-title":"Leuk Res"},{"key":"4254_CR3","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1182\/blood-2016-09-739086","volume":"132","author":"JE Cortes","year":"2018","unstructured":"Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre PD, Paquette R, Chuah C, et al. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018;132:393\u2013404.","journal-title":"Blood"},{"key":"4254_CR4","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.leukres.2016.07.007","volume":"48","author":"DJ Dorer","year":"2016","unstructured":"Dorer DJ, Knickerbocker RK, Baccarani M, Cortes JE, Hochhaus A, Talpaz M, et al. Impact of dose intensity of ponatinib on selected adverse events: multivariate analyses from a pooled population of clinical trial patients. Leuk Res. 2016;48:84\u201391.","journal-title":"Leuk Res"},{"key":"4254_CR5","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1093\/jjco\/hyae061","volume":"54","author":"N Takahashi","year":"2024","unstructured":"Takahashi N, Kondo T, Ikari Y, Fukumoto Y, Hatake K, Masunari A, et al. Real-world outcomes of ponatinib treatment in 724 patients with CML and Ph+ ALL: a post-marketing surveillance study with a special interest in arterial occlusive events in Japan. Jpn J Clin Oncol. 2024;54:930\u20138.","journal-title":"Jpn J Clin Oncol"}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-026-04254-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-026-04254-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-026-04254-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:59:26Z","timestamp":1791194366000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-026-04254-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":5,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["4254"],"URL":"https:\/\/doi.org\/10.1007\/s12185-026-04254-7","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]},"assertion":[{"value":"12 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 July 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"N.T. received honoraria (lecture fees), research grants, and consulting fees from Novartis Pharma K.K., and Otsuka Pharmaceutical Co., Ltd.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}