{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T13:40:14Z","timestamp":1776692414137,"version":"3.51.2"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007723","name":"Takeda Pharmaceuticals U.S.A.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007723","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In the phase 3 ponatinib\u20103001 trial (PhALLCON, NCT03589326), ponatinib demonstrated superior efficacy over imatinib with comparable safety in patients with newly diagnosed Philadelphia\u2010positive acute lymphoblastic leukemia (Ph+ ALL). This post hoc analysis evaluated the net benefits of ponatinib using a quality\u2010adjusted time without symptoms of disease or toxicity (Q\u2010TWiST) approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Overall survival (OS) time for patients from PhALLCON was partitioned into three health states: TOX (time with grade 3+ treatment\u2010emergent adverse events [TEAEs] before disease progression), TWiST (time without toxicity before progression), and REL (time from progression until death or end of follow\u2010up). Q\u2010TWiST was calculated as the sum of health utility\u2010weighted restricted mean durations of the three states. A relative Q\u2010TWiST gain of \u2265\u200910% was considered clinically important. Sensitivity analyses were conducted by varying TOX and REL utilities, follow\u2010up time, and the TOX definition (using grade 2+ TEAEs or patient\u2010perceived treatment tolerability assessed by the FACT\u2010GP5).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among all randomized patients (ponatinib <jats:italic>n<\/jats:italic>\u2009=\u2009164, imatinib <jats:italic>n<\/jats:italic>\u2009=\u200981), restricted mean OS was similar between arms (1082.2 vs. 1024.8\u2009days; <jats:italic>p<\/jats:italic>\u2009=\u20090.373). In the base\u2010case analysis, mean TWiST was 214.5\u2009days longer with ponatinib versus imatinib (95% CI 70.3\u2013358.7; <jats:italic>p<\/jats:italic>\u2009=\u20090.004), REL was shorter by 175.9\u2009days (325.4\u201326.5; <jats:italic>p<\/jats:italic>\u2009=\u20090.021), and TOX was not significantly different between arms (<jats:italic>p<\/jats:italic>\u2009=\u20090.228). The relative Q\u2010TWiST gain (10.98%) was clinically important. Sensitivity analyses consistently supported the robustness of the base\u2010case findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Ponatinib may prolong quality\u2010adjusted survival compared with imatinib, supporting the benefit\u2013risk profile of ponatinib as a front\u2010line treatment for Ph+ ALL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>NCT03589326<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70780","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T02:41:27Z","timestamp":1743561687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quality\u2010Adjusted Time Without Symptoms of Disease or Toxicity (Q\u2010<scp>TWiST<\/scp>) in Patients With Newly Diagnosed Philadelphia Chromosome\u2010Positive Acute Lymphoblastic Leukemia: A Comparison of Ponatinib Versus Imatinib"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3731-0769","authenticated-orcid":false,"given":"Ajibade","family":"Ashaye","sequence":"first","affiliation":[{"name":"Takeda Development Center Americas Inc.  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Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9564-4498","authenticated-orcid":false,"given":"Ibrahim","family":"Aldoss","sequence":"additional","affiliation":[{"name":"City of Hope National Medical Center  Duarte California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pau","family":"Montesinos","sequence":"additional","affiliation":[{"name":"Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9779-6217","authenticated-orcid":false,"given":"Pankit","family":"Vachhani","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanderson","family":"Rocha","sequence":"additional","affiliation":[{"name":"Instituto Do C\u00e2ncer Do Estado de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Papayannidis","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna, Istituto di Ematologia \u201cL. e A. 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