{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T18:25:49Z","timestamp":1784917549682,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008373","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008373","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ponatinib is a third\u2010generation BCR::ABL1 tyrosine kinase inhibitor (TKI) with robust activity in Philadelphia chromosome\u2013positive leukemias. Herein, we report the long\u2010term follow\u2010up of the phase 2 trial of ponatinib in chronic myeloid leukemia in chronic phase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients received ponatinib 30 to 45 mg\/day. The primary end point was the rate of 6\u2010month complete cytogenetic response (CCyR). The study was held in June 2014 because of the risk of cardiovascular toxicity, requiring patients to change TKI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty\u2010one patients were treated with ponatinib (median dose, 45 mg\/day). Median age was 48 years (range, 21\u201375); 30 (59%) had baseline cardiovascular comorbidities. Median treatment duration was 13 months (range, 2\u201325). Fourteen patients (28%) discontinued ponatinib because of toxicities, 36 (71%) after the Food and Drug Administration warning\/study closure, and one for noncompliance. Dasatinib was the most frequently chosen second\u2010line TKI (<jats:italic>n<\/jats:italic>\u00a0=\u00a034; 66%). Among 46 patients evaluable at 6 months, 44 (96%) achieved CCyR, 37 (80%) major molecular response, 28 (61%) MR4, and 21 (46%) MR4.5. The cumulative 6\u2010month rates of CCyR, major molecular response, MR4, and MR4.5 were 96%, 78%, 50%, and 36%, respectively. Durable MR4 \u226524 or \u226560 months was observed in 67% and 51% of patients, respectively. The 24\u2010month event\u2010free survival rate was 97%. After a median follow\u2010up of 128 months, the 10\u2010year overall survival rate was 90%. Eight patients (16%) had serious grade 2 to 3 cardiovascular adverse events, leading to permanent discontinuation in five (10%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Ponatinib yielded high cytogenetic and molecular responses in newly diagnosed chronic myeloid leukemia in chronic phase. Its use in the frontline setting is hindered by arterio\u2010\/vaso\u2010occlusive and other severe toxicities.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35384","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T08:53:55Z","timestamp":1716886435000},"page":"3344-3352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Results of ponatinib as frontline therapy for chronic myeloid leukemia in chronic phase"],"prefix":"10.1002","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9702-8485","authenticated-orcid":false,"given":"Fadi G.","family":"Haddad","sequence":"first","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9140-0610","authenticated-orcid":false,"given":"Koji","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3202-4878","authenticated-orcid":false,"given":"Lewis","family":"Nasr","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2983-2738","authenticated-orcid":false,"given":"Nicholas J.","family":"Short","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9892-9832","authenticated-orcid":false,"given":"Tapan","family":"Kadia","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Dellasala","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Cortes","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center Augusta University  Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3192-4199","authenticated-orcid":false,"given":"Franck E.","family":"Nicolini","sequence":"additional","affiliation":[{"name":"Department of Clinical Hematology and INSERM U1052 CRCL Centre Leon B\u00e9rard  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghayas C.","family":"Issa","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4465-6119","authenticated-orcid":false,"given":"Elias","family":"Jabbour","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-3307","authenticated-orcid":false,"given":"Hagop","family":"Kantarjian","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.09.028"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1205127"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1306494"},{"key":"e_1_2_11_5_1","unstructured":"UfaDA.ICLUSIG (ponatinib) tablets for oral use;2012."},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2019\u20100653"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyab040"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2016.34.15_suppl.7013"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012082"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010024\u201002159\u20100"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102016\u201009\u2010739086"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2352\u20103026(15)00127\u20101"},{"key":"e_1_2_11_13_1","unstructured":"Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0; 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