{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:01:56Z","timestamp":1790946116527,"version":"4.1.0"},"reference-count":48,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,22]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Chronic myeloid leukemia (CML) has served as a paradigm for the development of effective initial and next-generation targeted therapies. The availability of 5 effective and generally well-tolerated BCR::ABL1 tyrosine kinase inhibitors for the treatment of newly diagnosed chronic-phase CML offers patients and their treating physicians a welcome luxury of choice. The long-term outlook for patients with newly diagnosed chronic-phase CML is excellent, with expected survival similar to age-matched controls. However, most patients are expected to require lifelong treatment. As a result, important considerations when choosing frontline treatment include not only treatment efficacy but also response durability, tolerability, maximizing quality of life, avoidance of serious and irreversible toxicities, the ease of treatment administration, and, increasingly, the cost of treatment to the patient as well as to society.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024026508","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T15:59:03Z","timestamp":1744819143000},"page":"329-336","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":1,"title":["How I individualize frontline treatment for chronic-phase CML"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0033-2987","authenticated-orcid":false,"given":"Ariel","family":"Leyte-Vidal","sequence":"first","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL"},{"name":"2Division of Hematology\/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4398-3388","authenticated-orcid":false,"given":"Neil P.","family":"Shah","sequence":"additional","affiliation":[{"name":"2Division of Hematology\/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"5","key":"2026012211222059100_bib1","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/s41375-018-0341-4","article-title":"The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview","volume":"33","author":"Baccarani","year":"2019","journal-title":"Leukemia"},{"issue":"suppl 1","key":"2026012211222059100_bib2","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1016\/j.leukres.2003.10.005","article-title":"Mechanisms of transformation by the BCR-ABL oncogene: new perspectives in the post-imatinib era","volume":"28","author":"Van Etten","year":"2004","journal-title":"Leuk Res"},{"issue":"18","key":"2026012211222059100_bib3","doi-asserted-by":"crossref","first-page":"8120","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"},{"issue":"7280","key":"2026012211222059100_bib4","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/nature08675","article-title":"Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors","volume":"463","author":"Zhang","year":"2010","journal-title":"Nature"},{"issue":"6","key":"2026012211222059100_bib5","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.molcel.2006.01.035","article-title":"Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase","volume":"21","author":"Nagar","year":"2006","journal-title":"Mol Cell"},{"issue":"9","key":"2026012211222059100_bib6","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1038\/s41375-024-02353-0","article-title":"Absence of ABL1 exon 2-encoded SH3 residues in BCR::ABL1 destabilizes the autoinhibited kinase conformation and confers resistance to asciminib","volume":"38","author":"Leyte-Vidal","year":"2024","journal-title":"Leukemia"},{"issue":"9","key":"2026012211222059100_bib7","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1038\/s41375-024-02314-7","article-title":"The e13a3 (b2a3) and e14a3 (b3a3) BCR::ABL1 isoforms are resistant to asciminib","volume":"38","author":"Leske","year":"2024","journal-title":"Leukemia"},{"issue":"1","key":"2026012211222059100_bib8","doi-asserted-by":"crossref","first-page":"43","DOI":"10.6004\/jnccn.2024.0007","article-title":"Chronic myeloid leukemia, version 2.2024, NCCN Clinical Practice Guidelines in Oncology","volume":"22","author":"Shah","year":"2024","journal-title":"J Natl Compr Canc Netw"},{"issue":"4","key":"2026012211222059100_bib9","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s41375-020-0776-2","article-title":"European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia","volume":"34","author":"Hochhaus","year":"2020","journal-title":"Leukemia"},{"issue":"35","key":"2026012211222059100_bib10","doi-asserted-by":"crossref","first-page":"6041","DOI":"10.1200\/JCO.2009.25.0779","article-title":"Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet","volume":"27","author":"Baccarani","year":"2009","journal-title":"J Clin Oncol"},{"issue":"20","key":"2026012211222059100_bib11","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"issue":"7","key":"2026012211222059100_bib12","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic\/dendritic neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"issue":"9","key":"2026012211222059100_bib13","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1200\/JCO.23.01689","article-title":"CML and the WHO: why? [published correction appears in J Clin Oncol. 2024;42(32):3885]","volume":"42","author":"Berman","year":"2024","journal-title":"J Clin Oncol"},{"key":"2026012211222059100_bib14","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.leukres.2017.06.009","article-title":"Exome sequencing reveals DNMT3A and ASXL1 variants associate with progression of chronic myeloid leukemia after tyrosine kinase inhibitor therapy","volume":"59","author":"Kim","year":"2017","journal-title":"Leuk Res"},{"issue":"18","key":"2026012211222059100_bib15","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1182\/bloodadvances.2017006825","article-title":"ASXL1 and BIM germ line variants predict response and identify CML patients with the greatest risk of imatinib failure","volume":"1","author":"Marum","year":"2017","journal-title":"Blood Adv"},{"issue":"9","key":"2026012211222059100_bib16","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1182\/blood-2018-02-832253","article-title":"Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease","volume":"132","author":"Branford","year":"2018","journal-title":"Blood"},{"key":"2026012211222059100_bib17","doi-asserted-by":"crossref","first-page":"8581","DOI":"10.2147\/OTT.S257661","article-title":"Integrative genomic analysis reveals cancer-associated gene mutations in chronic myeloid leukemia patients with resistance or intolerance to tyrosine kinase inhibitor","volume":"13","author":"Wu","year":"2020","journal-title":"Onco Targets Ther"},{"issue":"9","key":"2026012211222059100_bib18","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1038\/s41375-022-01648-4","article-title":"ASXL1 mutations predict inferior molecular response to nilotinib treatment in chronic myeloid leukemia","volume":"36","author":"Sch\u00f6nfeld","year":"2022","journal-title":"Leukemia"},{"issue":"10","key":"2026012211222059100_bib19","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41408-022-00742-1","article-title":"Prognostic impact of ASXL1 mutations in chronic phase chronic myeloid leukemia","volume":"12","author":"Bidikian","year":"2022","journal-title":"Blood Cancer J"},{"issue":"20","key":"2026012211222059100_bib20","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1200\/JCO.2015.64.8899","article-title":"Final 5-year study results of DASISION: the Dasatinib Versus Imatinib Study in Treatment-Na\u00efve Chronic Myeloid Leukemia Patients trial","volume":"34","author":"Cortes","year":"2016","journal-title":"J Clin Oncol"},{"issue":"2","key":"2026012211222059100_bib21","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/s41375-020-01111-2","article-title":"Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis [published correction appears in Leukemia. 2021;35(7):2142-2143]","volume":"35","author":"Kantarjian","year":"2021","journal-title":"Leukemia"},{"issue":"5682","key":"2026012211222059100_bib22","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1126\/science.1099480","article-title":"Overriding imatinib resistance with a novel ABL kinase inhibitor","volume":"305","author":"Shah","year":"2004","journal-title":"Science"},{"issue":"11","key":"2026012211222059100_bib23","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1158\/0008-5472.CAN-05-0259","article-title":"In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants","volume":"65","author":"O'Hare","year":"2005","journal-title":"Cancer Res"},{"issue":"24","key":"2026012211222059100_bib24","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1056\/NEJMoa1002315","article-title":"Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia","volume":"362","author":"Kantarjian","year":"2010","journal-title":"N Engl J Med"},{"issue":"24","key":"2026012211222059100_bib25","doi-asserted-by":"crossref","first-page":"2251","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"},{"issue":"10","key":"2026012211222059100_bib26","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1056\/NEJMoa2400858","article-title":"Asciminib in newly diagnosed chronic myeloid leukemia","volume":"391","author":"Hochhaus","year":"2024","journal-title":"N Engl J Med"},{"issue":"7","key":"2026012211222059100_bib27","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1038\/s41375-022-01589-y","article-title":"Bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: final results from the BFORE trial","volume":"36","author":"Br\u00fcmmendorf","year":"2022","journal-title":"Leukemia"},{"issue":"3","key":"2026012211222059100_bib28","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1200\/JCO.2017.75.4663","article-title":"Front-line treatment options for chronic-phase chronic myeloid leukemia","volume":"36","author":"Shah","year":"2018","journal-title":"J Clin Oncol"},{"issue":"10","key":"2026012211222059100_bib29","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.3324\/haematol.2023.283428","article-title":"Treatment of chronic-phase chronic myeloid leukemia in patients randomized to dasatinib or imatinib after suboptimal responses to 3 months of imatinib therapy: final 5-year results from DASCERN","volume":"109","author":"Cortes","year":"2024","journal-title":"Haematologica"},{"issue":"6","key":"2026012211222059100_bib30","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S1470-2045(18)30192-X","article-title":"Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial","volume":"19","author":"Saussele","year":"2018","journal-title":"Lancet Oncol"},{"issue":"16","key":"2026012211222059100_bib31","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1200\/JCO.23.01647","article-title":"European Stop Tyrosine Kinase Inhibitor trial (EURO-SKI) in chronic myeloid leukemia: final analysis and novel prognostic factors for treatment-free remission","volume":"42","author":"Mahon","year":"2024","journal-title":"J Clin Oncol"},{"issue":"10","key":"2026012211222059100_bib32","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.clml.2023.05.009","article-title":"Low-dose dasatinib (50 mg daily) frontline therapy in newly diagnosed chronic phase chronic myeloid leukemia: 5-year follow-up results","volume":"23","author":"Gener-Ricos","year":"2023","journal-title":"Clin Lymphoma Myeloma Leuk"},{"issue":"3","key":"2026012211222059100_bib33","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1200\/JCO.2009.25.4920","article-title":"Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia","volume":"28","author":"Cortes","year":"2010","journal-title":"J Clin Oncol"},{"issue":"11","key":"2026012211222059100_bib34","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1002\/ajh.26689","article-title":"Low-dose dasatinib 50 mg\/day versus standard-dose dasatinib 100 mg\/day as frontline therapy in chronic myeloid leukemia in chronic phase: a propensity score analysis","volume":"97","author":"Jabbour","year":"2022","journal-title":"Am J Hematol"},{"issue":"6","key":"2026012211222059100_bib35","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.clml.2017.02.023","article-title":"Elderly patients with chronic myeloid leukemia benefit from a dasatinib dose as low as 20 mg","volume":"17","author":"Itamura","year":"2017","journal-title":"Clin Lymphoma Myeloma Leuk"},{"issue":"12","key":"2026012211222059100_bib36","doi-asserted-by":"crossref","first-page":"e902","DOI":"10.1016\/S2352-3026(21)00333-1","article-title":"Low-dose dasatinib in older patients with chronic myeloid leukaemia in chronic phase (DAVLEC): a single-arm, multicentre, phase 2 trial","volume":"8","author":"Murai","year":"2021","journal-title":"Lancet Haematol"},{"issue":"1","key":"2026012211222059100_bib37","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3324\/haematol.2018.188987","article-title":"Incidence, outcomes, and risk factors of pleural effusion in patients receiving dasatinib therapy for Philadelphia chromosome-positive leukemia","volume":"104","author":"Hughes","year":"2019","journal-title":"Haematologica"},{"issue":"20","key":"2026012211222059100_bib38","doi-asserted-by":"crossref","first-page":"5237","DOI":"10.1182\/bloodadvances.2024012655","article-title":"Nilotinib vs dasatinib in achieving MR4.5 for de novo chronic myeloid leukemia: the randomized JALSG CML212 study","volume":"8","author":"Matsumura","year":"2024","journal-title":"Blood Adv"},{"issue":"4","key":"2026012211222059100_bib39","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1182\/blood-2010-03-277152","article-title":"Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results","volume":"117","author":"Kantarjian","year":"2011","journal-title":"Blood"},{"issue":"21","key":"2026012211222059100_bib40","doi-asserted-by":"crossref","first-page":"2031","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"},{"issue":"suppl 1","key":"2026012211222059100_bib41","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1182\/blood-2024-203757","article-title":"Asciminib (ASC) demonstrates favorable safety and tolerability compared with each investigator-selected tyrosine kinase inhibitor (IS TKI) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) in the pivotal phase 3 ASC4FIRST study [abstract]","volume":"144","author":"Cortes","year":"2024","journal-title":"Blood"},{"issue":"6","key":"2026012211222059100_bib42","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1177\/0091270009333854","article-title":"Phase I study of the effect of gastric acid pH modulators on the bioavailability of oral dasatinib in healthy subjects","volume":"49","author":"Eley","year":"2009","journal-title":"J Clin Pharmacol"},{"issue":"20","key":"2026012211222059100_bib43","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1038\/leu.2014.153","article-title":"Velocity of early BCR-ABL transcript elimination as an optimal predictor of outcome in chronic myeloid leukemia patients in chronic phase on treatment with imatinib","volume":"28","author":"Hanfstein","year":"2014","journal-title":"Leukemia"},{"issue":"2","key":"2026012211222059100_bib44","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/s41375-019-0563-0","article-title":"Health-related quality of life of newly diagnosed chronic myeloid leukemia patients treated with first-line dasatinib versus imatinib therapy","volume":"34","author":"Efficace","year":"2020","journal-title":"Leukemia"},{"issue":"11","key":"2026012211222059100_bib45","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1185\/03007995.2014.944973","article-title":"Impact of low-grade adverse events on health-related quality of life in adult patients receiving imatinib or nilotinib for newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase","volume":"30","author":"Gu\u00e9rin","year":"2014","journal-title":"Curr Med Res Opin"},{"issue":"38","key":"2026012211222059100_bib46","doi-asserted-by":"crossref","first-page":"4161","DOI":"10.2217\/fon-2022-0923","article-title":"Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial","volume":"18","author":"Cortes","year":"2022","journal-title":"Future Oncol"},{"issue":"6","key":"2026012211222059100_bib47","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1182\/blood.2023022538","article-title":"BCR::ABL1 kinase N-lobe mutants confer moderate to high degrees of resistance to asciminib","volume":"144","author":"Leyte-Vidal","year":"2024","journal-title":"Blood"},{"issue":"11","key":"2026012211222059100_bib48","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1038\/s41375-024-02411-7","article-title":"Impact of BCR::ABL1 single nucleotide variants on asciminib efficacy","volume":"38","author":"Innes","year":"2024","journal-title":"Leukemia"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/147\/4\/329\/2497693\/blood_bld-2024-026508-c-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/147\/4\/329\/2497693\/blood_bld-2024-026508-c-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T16:22:34Z","timestamp":1769098954000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/147\/4\/329\/536757\/How-I-individualize-frontline-treatment-for"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":48,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,1,22]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2024026508","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1,22]]},"published":{"date-parts":[[2026,1,22]]}}}