{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T01:11:16Z","timestamp":1784941876182,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Ponatinib and asciminib are approved for third-line therapy in chronic-phase chronic myeloid leukemia (CP-CML) and are the only drugs approved for patients with the T315I mutation in the United States. In Europe, only ponatinib is approved for patients with the T315I mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical trials evaluating ponatinib or asciminib in patients with relapsed and refractory (R\/R) CP-CML who failed one or more second-generation TKIs or had the T315I mutation were identified in a systematic review of medical literature databases. A matching-adjusted indirect comparison (MAIC) analysis with individual patient-level data with ponatinib was used to balance baseline characteristics between ponatinib and asciminib groups. After matching, the response rate was calculated using the MAIC weight for each patient and the difference in response rate was calculated using a two-independent proportion Z-test. Cumulative rates of <jats:italic>BCR::ABL1<\/jats:italic><jats:sup>IS<\/jats:sup> \u22641% and major molecular response (MMR) in patients without baseline response were compared. Patients were further stratified by T315I mutation status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The MAIC included four trials (ponatinib: NCT02467270, NCT01207440; asciminib: NCT02081378, NCT03106779). In patients without baseline response of <jats:italic>BCR::ABL1<\/jats:italic><jats:sup>IS<\/jats:sup> \u22641%, the adjusted <jats:italic>BCR::ABL1<\/jats:italic><jats:sup>IS<\/jats:sup> \u22641% rate difference with ponatinib vs. asciminib was 9.33% (95% confidence interval [CI]: 0.79%\u201317.86%; adjusted MMR rate difference: 6.84% [95% CI: \u22120.95%\u201314.62%]) by 12 months in favor of ponatinib. In patients with the T315I mutation, adjusted <jats:italic>BCR::ABL1<\/jats:italic><jats:sup>IS<\/jats:sup> \u22641% rate difference with ponatinib vs. asciminib was 43.54% (95% CI: 22.20%\u201364.87%; adjusted MMR rate difference: 47.37% [95% CI: 28.72%\u201366.02%]) by 12 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>After key baseline characteristics adjustment, cumulative <jats:italic>BCR::ABL1<\/jats:italic><jats:sup>IS<\/jats:sup> \u22641% and MMR rates were statistically higher with ponatinib than asciminib in patients without a baseline response in most of the comparisons by 12 months. Favorable efficacy outcomes observed in ponatinib vs. asciminib were consistently stronger in the T315I mutation subgroup.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2024.1455378","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T11:55:22Z","timestamp":1732103722000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Ponatinib vs. asciminib in post\u2013second-generation tyrosine kinase inhibitor therapy for chronic-phase chronic myeloid leukemia: a matching-adjusted indirect comparison"],"prefix":"10.3389","volume":"14","author":[{"given":"Valentin","family":"Garcia-Gutierrez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajibade","family":"Ashaye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehul","family":"Dalal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Laliman-Khara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Breccia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Rutherford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoora","family":"Moradian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros","family":"Patos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias Joseph","family":"Jabbour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"B1","unstructured":"American Cancer Society\n          Cancer Facts & Figures\u00a02023\n          \n          2023"},{"key":"B2","unstructured":"Phases of Chronic Myeloid Leukemia\n          \n          2023"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2020.004710.6004\/jnccn.2020.0047","article-title":"Chronic myeloid leukemia, version 2.2021, NCCN clinical practice guidelines in oncology","volume":"18","author":"Deininger","year":"2020","journal-title":"J Natl Compr Canc Netw"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/s2352-3026(15)00048-410.1016\/S2352-3026(15)00048-4","article-title":"Relative survival in patients with chronic-phase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials","volume":"2","author":"Sasaki","year":"2015","journal-title":"Lancet Haematol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01040","article-title":"Discovery of asciminib (ABL001), an allosteric inhibitor of the tyrosine kinase activity of BCR-ABL1","volume":"61","author":"Schoepfer","year":"2018","journal-title":"J Med Chem"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nature2170210.1038\/nature21702","article-title":"The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1","volume":"543","author":"Wylie","year":"2017","journal-title":"Nature"},{"key":"B7","article-title":"Current treatment approaches for chronic myelogenous leukemia","author":"Druker","year":"2001","journal-title":"Cancer J"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912614","article-title":"Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia","volume":"362","author":"Saglio","year":"2010","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-08068910.1182\/blood-2007-03-080689","article-title":"Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance","volume":"110","author":"Kantarjian","year":"2007","journal-title":"Blood"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2017.74.7162","article-title":"Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial","volume":"36","author":"Cortes","year":"2017","journal-title":"J Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-376087","article-title":"Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION)","volume":"119","author":"Kantarjian","year":"2012","journal-title":"Blood"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V114.22.1126.1126","article-title":"International randomized study of interferon vs STI571 (IRIS) 8-year follow up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib","volume":"114","author":"Deininger","year":"2009","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2010.28.15_suppl.6512","article-title":"Four-year follow-up of patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving 100 mg of dasatinib once daily","volume":"28","author":"Shah","year":"2010","journal-title":"J Clin Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.09.02810.1016\/j.ccr.2009.09.028","article-title":"AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance","volume":"16","author":"O\u2019Hare","year":"2009","journal-title":"Cancer Cell"},{"key":"B15","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.leukres.2013.09.011","article-title":"Implications of BCR-ABL1 kinase domain-mediated resistance in chronic myeloid leukemia","volume":"38","author":"Soverini","year":"2014","journal-title":"Leuk Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012082","article-title":"Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial","volume":"138","author":"Cortes","year":"2021","journal-title":"Blood"},{"key":"B17","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1182\/blood-2016-09-739086","article-title":"Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial","volume":"132","author":"Cortes","year":"2018","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1902328","article-title":"Asciminib in chronic myeloid leukemia after ABL kinase inhibitor failure","volume":"381","author":"Hughes","year":"2019","journal-title":"N Engl J Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"4536","DOI":"10.1182\/blood-2023-186854","article-title":"Sustained Efficacy and Safety with Asciminib (ASC) after Almost 4 Years of Median Follow-up from Ascembl, a Phase 3 Study of ASC Vs Bosutinib (BOS) in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) after \u22652 Prior Tyrosine Kinase Inhibitors (TKIs): An End of Study Treatment (EOS Tx) Update, Including Results from Switch Population","volume":"142","author":"Mauro","year":"2023","journal-title":"Blood"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009984","article-title":"A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs","volume":"138","author":"R\u00e9a","year":"2021","journal-title":"Blood"},{"key":"B21","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1182\/blood-2023-187322","article-title":"With up to 8 years of therapy, asciminib (ASC) monotherapy demonstrated continued favorable efficacy, safety, and tolerability in patients (Pts) with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) without the T315I mutation: Final results from the phase 1 X2101 study","volume":"142","author":"Hochhaus","year":"2023","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306494","article-title":"A phase 2 trial of ponatinib in Philadelphia chromosome\u2013positive leukemias","volume":"369","author":"Cortes","year":"2013","journal-title":"N Engl J Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2012.05.00410.1016\/j.jval.2012.05.004","article-title":"Matching-adjusted indirect comparisons: a new tool for timely comparative effectiveness research","volume":"15","author":"Signorovitch","year":"2012","journal-title":"Value Health"},{"key":"B24","article-title":"NICE DSU technical support document 18: methods for population-adjusted indirect comparisons in submissions to NICE","author":"Phillippo","year":"2016"},{"key":"B25","article-title":"Asciminib and ponatinib exert synergistic anti-neoplastic effects on CML cells expressing BCR-ABL1 (T315I)-compound mutations","volume":"11","author":"Gleixner","year":"2021","journal-title":"Am J Cancer Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/s41408-023-00823-910.1038\/s41408-023-00823-9","article-title":"Management of chronic myeloid leukemia in 2023 - common ground and common sense","volume":"13","author":"Senapati","year":"2023","journal-title":"Blood Cancer J"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.04.06010.1016\/j.bmcl.2011.04.060","article-title":"Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant","volume":"21","author":"Thomas","year":"2011","journal-title":"Bioorg Med Chem Lett"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.2147\/ott.S189391","article-title":"Ponatinib: a novel multi-tyrosine kinase inhibitor against human malignancies","volume":"12","author":"Tan","year":"2019","journal-title":"Onco Targets Ther"},{"key":"B29","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.leukres.2014.10.005","article-title":"Comparative efficacy of tyrosine kinase inhibitor treatments in the third-line setting, for chronic-phase chronic myelogenous leukemia after failure of second-generation tyrosine kinase inhibitors","volume":"39","author":"Lipton","year":"2015","journal-title":"Leuk Res"},{"key":"B30","article-title":"Number needed to treat and cost per response achieved among patients with relapsed\/refractory chronic-phase chronic myeloid leukemia managed with ponatinib or asciminib","author":"Jabbour","year":"2022"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-022-04562-510.1007\/s00432-022-04562-5","article-title":"Matching-adjusted indirect comparison of asciminib versus other treatments in chronic-phase chronic myeloid leukemia after failure of two prior tyrosine kinase inhibitors","volume":"149","author":"Atallah","year":"2023","journal-title":"J Cancer Res Clin Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02159-0","article-title":"Dose modification dynamics of ponatinib in patients with chronic-phase chronic myeloid leukemia (CP-CML) from the PACE and OPTIC trials","volume":"38","author":"Jabbour","year":"2024","journal-title":"Leukemia"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-023-01860-w","article-title":"Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results","volume":"37","author":"Mauro","year":"2023","journal-title":"Leukemia"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1205127","article-title":"Ponatinib in refractory Philadelphia chromosome-positive leukemias","volume":"367","author":"Cortes","year":"2012","journal-title":"N Engl J Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/s2352-3026(15)00127-1","article-title":"Ponatinib as first-line treatment for patients with chronic myeloid leukaemia in chronic phase: a phase 2 study","volume":"2","author":"Jain","year":"2015","journal-title":"Lancet Haematol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1097\/01.HS9.0000845700.84142.c0","article-title":"Asciminib provides durable molecular responses in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) with the T315I mutation: updated efficacy and safety data from a phase I trial [abstract P704]","volume":"6","author":"Hughes","year":"2022","journal-title":"HemaSphere"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26852","article-title":"The outcomes of patients with chronic myeloid leukemia treated with third-line BCR::ABL1 tyrosine kinase inhibitors","volume":"98","author":"Jabbour","year":"2023","journal-title":"Am J Hematol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.7004","article-title":"Efficacy and safety results from ASCEMBL, a phase 3 study of asciminib versus bosutinib (BOS) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after \u22652 prior tyrosine kinase inhibitors (TKIs): Week 96 update","volume":"40","author":"Rea","year":"2022","journal-title":"J Clin Oncol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2668610.1002\/ajh.26686","article-title":"Ponatinib after failure of second-generation tyrosine kinase inhibitor in resistant chronic-phase chronic myeloid leukemia","volume":"97","author":"Kantarjian","year":"2022","journal-title":"Am J Hematol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1455378\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T11:55:26Z","timestamp":1732103726000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1455378\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":39,"alternative-id":["10.3389\/fonc.2024.1455378"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2024.1455378","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]},"article-number":"1455378"}}