{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:48:46Z","timestamp":1790880526730,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ponatinib, the only third\u2010generation pan\u2010BCR::ABL1 inhibitor with activity against all known <jats:italic>BCR::ABL1<\/jats:italic> mutations including T315I, has demonstrated deep and durable responses in patients with chronic\u2010phase chronic myeloid leukemia (CP\u2010CML) resistant to prior second\u2010generation (2G) TKI treatment. We present efficacy and safety outcomes from the Ponatinib Philadelphia chromosome\u2013positive acute lymphoblastic leukemia (Ph+\u2009ALL) and CML Evaluation (PACE) and Optimizing Ponatinib Treatment in CP\u2010CML (OPTIC) trials for this patient population. PACE (NCT01207440) evaluated ponatinib 45\u2009mg\/day in CML patients with resistance to prior TKI or T315I. In OPTIC (NCT02467270), patients with CP\u2010CML and resistance to \u22652 prior TKIs or T315I receiving 45 or 30\u2009mg\/day reduced their doses to 15\u2009mg\/day upon achieving \u22641% <jats:italic>BCR::ABL1<\/jats:italic><jats:sup>IS<\/jats:sup> or received 15\u2009mg\/day continuously. Efficacy and safety outcomes from patients with CP\u2010CML treated with \u22651 2G TKI (PACE, <jats:italic>n<\/jats:italic>\u00a0=\u2009257) and OPTIC (<jats:italic>n<\/jats:italic>\u00a0=\u200993), 45\u2010mg starting dose cohort, were analyzed for <jats:italic>BCR::ABL1<\/jats:italic><jats:sup>IS<\/jats:sup> response rates, overall survival (OS), progression\u2010free survival (PFS), and safety. By 24\u2009months, the percentages of patients with \u22641% <jats:italic>BCR::ABL1<\/jats:italic><jats:sup>IS<\/jats:sup> response, PFS, and OS were 46%, 68%, and 85%, respectively, in PACE and 57%, 80%, and 91%, respectively, in OPTIC. Serious treatment\u2010emergent adverse events and serious treatment\u2010emergent arterial occlusive event rates were 63% and 18% in PACE and 34% and 4% in OPTIC. Ponatinib shows high response rates and robust survival outcomes in patients whose disease failed prior to 2G TKIs, including patients with T315I mutation. The response\u2010based dosing in OPTIC led to improved safety and similar efficacy outcomes compared with PACE.<\/jats:p>","DOI":"10.1002\/ajh.26686","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T14:34:02Z","timestamp":1660314842000},"page":"1419-1426","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Ponatinib after failure of <scp>second\u2010generation<\/scp> tyrosine kinase inhibitor in resistant <scp>chronic\u2010phase<\/scp> chronic myeloid leukemia"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-3307","authenticated-orcid":false,"given":"Hagop M.","family":"Kantarjian","sequence":"first","affiliation":[{"name":"Department of Leukemia The University of Texas MD 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 MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Deininger","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine University of Utah Huntsman Cancer Institute  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Abruzzese","sequence":"additional","affiliation":[{"name":"Division of Hematology, S. Eugenio Hospital Tor Vergata University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Apperley","sequence":"additional","affiliation":[{"name":"Centre for Haematology Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-1071","authenticated-orcid":false,"given":"Jorge","family":"Cortes","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center  Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Chuah","sequence":"additional","affiliation":[{"name":"Department of Haematology Singapore General Hospital, Duke\u2010NUS Medical School  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"DeAngelo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"DiPersio","sequence":"additional","affiliation":[{"name":"Division of Oncology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hochhaus","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Universit\u00e4tsklinikum Jena  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Lipton","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3779-1996","authenticated-orcid":false,"given":"Franck E.","family":"Nicolini","sequence":"additional","affiliation":[{"name":"Centre Leon Berard, Department d'H\u00e9matologie &amp; INSERM U1052 Equipe BMP, Niche Tumorale et Resistance, CRCL  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Pinilla\u2010Ibarz","sequence":"additional","affiliation":[{"name":"H. Lee Moffitt Cancer Center &amp; Research Institute  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Rea","sequence":"additional","affiliation":[{"name":"Department of Hematology Hopital Saint\u2010Louis  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianantonio","family":"Rosti","sequence":"additional","affiliation":[{"name":"IRST\/IRCCS \u201cDino Amadori\u201d  Meldola Province of Forl\u00ec\u2010Cesena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Rousselot","sequence":"additional","affiliation":[{"name":"Hospital Mignot University de Versailles Saint\u2010Quentin\u2010en\u2010Yvelines  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil P.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Medicine (Hematology\/Oncology) University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3361-3981","authenticated-orcid":false,"given":"Moshe","family":"Talpaz","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouryadeep","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc.  Lexington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Ren","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc.  Lexington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mauro","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25792"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24275"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-1484"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-066936"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-221531"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.080234"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2014.10.005"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.09.028"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306494"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012082"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-739086"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0776-2"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13108"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.5"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.8899"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-513937"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.110"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-01111-2"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-142954"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009984"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1902328"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.7326\/M15-0288"}],"updated-by":[{"DOI":"10.1002\/ajh.26894","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000}}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.26686","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajh.26686","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.26686","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T19:11:37Z","timestamp":1692472297000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.26686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,30]]},"references-count":22,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/ajh.26686"],"URL":"https:\/\/doi.org\/10.1002\/ajh.26686","archive":["Portico"],"relation":{"correction":[{"id-type":"doi","id":"10.1002\/ajh.26894","asserted-by":"object"}]},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,30]]},"assertion":[{"value":"2022-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}