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To explore the association between clinical response and HRQoL and substantiate the superior effect of ponatinib over imatinib on HRQoL, we analyzed the impact of clinical response and treatment tolerability on changes in HRQoL.<\/jats:p>\n                  <jats:p>HRQoL was assessed using the Functional Assessment of Cancer Therapy\u2013Leukemia (FACT-Leu) questionnaire and the EQ-5D-5\u00a0L. Treatment tolerability was assessed using the FACT-GP5 item \u201cbothered by treatment side effects.\u201d Linear mixed-effects regression models were used to examine changes in HRQoL over time, with clinical response status and patient-reported overall treatment tolerability as time-varying predictors, while controlling for significant covariates.<\/jats:p>\n                  <jats:p>\n                    This analysis included data from 238 patients (159 ponatinib, 79 imatinib). Achieving clinical response (complete remission or incomplete remission) was associated with significantly better changes from baseline across all FACT-Leu domains and the EQ-visual analogue scale than not achieving clinical response (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Treatment-related side effects led to significantly and meaningfully worse changes in HRQoL than \u201cnot bothered by treatment,\u201d with higher levels of \u201cbother\u201d associated with greater worsening in HRQoL from baseline.\n                  <\/jats:p>\n                  <jats:p>Taken together with the better treatment tolerability and longer response duration of ponatinib compared to imatinib, these findings further substantiate the HRQoL benefit of ponatinib over imatinib in patients with Ph\u2009+\u2009ALL.<\/jats:p>","DOI":"10.1007\/s00277-025-06635-0","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T09:52:06Z","timestamp":1760089926000},"page":"4669-4678","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of clinical response and treatment tolerability on HRQoL in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia patients treated with ponatinib or imatinib"],"prefix":"10.1007","volume":"104","author":[{"given":"Ajibade","family":"Ashaye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Aldoss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pau","family":"Montesinos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankit","family":"Vachhani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanderson","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Papayannidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica T.","family":"Leonard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria R.","family":"Baer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose-Maria","family":"Ribera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meliessa","family":"Hennessy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandar","family":"Vorog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shien","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"6635_CR1","unstructured":"National Cancer Institute (2024) Adult Acute Lymphoblastic Leukemia Treatment (PDQ\u00ae)\u2013Patient Version https:\/\/www.cancer.gov\/types\/leukemia\/hp\/adult-all-treatment-pdq. 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Data will be provided after de-identification, in compliance with applicable privacy laws, data protection, and requirements for consent and anonymization.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data sharing"}},{"value":"The PhALLCON trial was conducted in compliance with the informed consent regulations outlined in GCP. All patients completed the initial consent process before enrolling to the study. During this process, the person obtaining consent explained the study objectives and potential risks and benefits to patients using the ICF approved by the IRB\/IEC. Patients were given adequate time to ask questions and make a voluntary decision to participate. Each patient signed and dated the ICF before any protocol-specific procedures were performed.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent"}},{"value":"The study protocol for the PhALLCON trial was approved by the institutional review boards or ethics committees of all participating centers. The PhALLCON trial was conducted in compliance with United States (US) Title 21 Code of Federal Regulations (CFR) Parts 50, 54, 56, and 312; the International Council for Harmonisation (ICH) of Technical Requirements for Pharmaceuticals for Human Use Good Clinical Practice (GCP) Guideline E6; the Declaration of Helsinki; and applicable local regulations. The clinical study protocol and its amendments, as well as the informed consent form (ICF) and Investigator\u2019s Brochure, were reviewed and approved by the Institutional Review Board\/Independent Ethics Committee (IRB\/IEC) of the participating study centers.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Ajibade Ashaye, Yanyu Wu, Meliessa Hennessy, and Alexandar Vorog report employment by Takeda. Ling Shi and Shien Guo report employment by Evidera, which received funding for conducting the statistical analysis in this study. Ibrahim Aldoss reports honoraria from Takeda, Amgen, Pfizer, Jazz, Sobi, Kite, Syndax, and Adaptive; consulting\/advisory roles at Takeda, Amgen, Pfizer, Jazz, Sobi, Kite, Adaptive, and Syndax; participation in speakers bureau at Pfizer; and research funding from AbbVie and MacroGenics. Pau Montesinos reports consulting\/advisory roles at Takeda, Daiichi Sankyo, and Bristol Myers Squibb; participation in speakers bureau at Servier; and research funding from AbbVie, Takeda, Daiichi Sankyo, Novartis, and Servier. Pankit Vachhani reports consulting\/advisory roles at Abbvie, Amgen, Blueprint Medicines, Cogent Biosciences, Incyte, CTI BioPharma, Corp (now Sobi), Genentech, Geron, GlaxoSmith Kline, Karyopharm, Merck, MorphoSys, Novartis, Pfizer, Stemline, and Takeda. Vanderson Rocha reports consulting\/advisory roles at Pfizer, Takeda, AbbVie, Astellas, Kite, and Amgen. Cristina Papayannidis reports consulting\/advisory roles at AbbVie, Astellas, Novartis, Bristol Myers Squibb, Menarini Stemline, Blueprint Medicines, Incyte, GlaxoSmithKline, Amgen, Pfizer, and Janssen; and personal fees from Astellas, Novartis, Pfizer, and Amgen. Jessica T. Leonard reports consulting\/advisory roles at Adaptive Biotechnologies, Kite\/Gilead, Pfizer, and Takeda; and support for travel, accommodations, and expenses from Adaptive Biotechnologies. Maria R. Baer reports institutional research funding from AbbVie, Ascentage Pharma, Astellas, Curadev, FORMA Therapeutics, Kite\/Gilead, Kura Oncology, and Takeda. Jose-Maria Ribera reports consulting\/advisory roles at Incyte, Pfizer, Bristol Myers Squibb, Novartis, and Takeda; and research funding from Amgen.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}