{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:35:49Z","timestamp":1790908549891,"version":"4.1.0"},"reference-count":29,"publisher":"American Society of Hematology","issue":"19","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,11,7]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Asciminib is a myristoyl site BCR::ABL1 inhibitor approved for patients with chronic-phase chronic myeloid leukemia (CP-CML) failing \u22652 prior lines of therapy. The Australasian Leukaemia and Lymphoma Group conducted the Asciminib Evaluation in Newly Diagnosed CML study to assess efficacy of asciminib for newly diagnosed CP-CML. Patients commenced asciminib 40 mg twice daily. Patients with treatment failure, defined as BCR::ABL1 of &amp;gt;10% at 3 or 6 months, or &amp;gt;1% at 12 or 18 months, received either imatinib, nilotinib, or dasatinib in addition to asciminib. In patients with suboptimal response, defined as levels of 1% to 10% at 6 months, &amp;gt;0.1% to 1% at 12 months, or &amp;gt;0.01% to 1% at 18 months, the asciminib dose was increased to 80 mg twice daily. With a median follow-up of 21 months (range, 0-36), 82 of 101 patients continue asciminib. Most common reasons for treatment discontinuation were adverse events (6%), loss of response (4%), and withdrawn consent (5%). There were no deaths; 1 patient developed lymphoid blast crisis. The coprimary end points were early molecular response (BCR::ABL1 of \u226410% at 3 months), achieved in 93% (96% confidence interval [CI], 86-97%), and major molecular response by 12 months achieved in 79%; (95% CI, 70-87%), respectively. Cumulative incidence of molecular response 4.5 was 53% by 24 months. One patient had 2 cerebrovascular events; no other arterial occlusive events were reported. Asciminib as frontline CP-CML therapy leads to high rates of molecular response with excellent tolerance and a low rate of discontinuation for toxicity. This trial was registered at https:\/\/www.anzctr.org.au\/ as #ACTRN12620000851965.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024024657","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T16:09:19Z","timestamp":1722874159000},"page":"1993-2001","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":28,"title":["Asciminib monotherapy as frontline treatment of chronic-phase chronic myeloid leukemia: results from the ASCEND study"],"prefix":"10.1182","volume":"144","author":[{"given":"David T.","family":"Yeung","sequence":"first","affiliation":[{"name":"1Haematology Department, Royal Adelaide Hospital, Adelaide Medical School, University of Adelaide and Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5895-8797","authenticated-orcid":false,"given":"Naranie","family":"Shanmuganathan","sequence":"additional","affiliation":[{"name":"1Haematology Department, Royal Adelaide Hospital, Adelaide Medical School, University of Adelaide and Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8825-8625","authenticated-orcid":false,"given":"John","family":"Reynolds","sequence":"additional","affiliation":[{"name":"2The Alfred Hospital and Australian Centre for Blood Diseases, Monash University, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5095-7981","authenticated-orcid":false,"given":"Susan","family":"Branford","sequence":"additional","affiliation":[{"name":"3Department of Genetics and Molecular Pathology, SA Pathology and Centre for Cancer Biology, University of South Australia, and Adelaide Medical School, University of Adelaide, Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mannu","family":"Walia","sequence":"additional","affiliation":[{"name":"4Australasian Leukaemia and Lymphoma Group, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes S. M.","family":"Yong","sequence":"additional","affiliation":[{"name":"5Haematology Department, Royal Perth Hospital and University of Western Australia, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3185-6488","authenticated-orcid":false,"given":"Jake","family":"Shortt","sequence":"additional","affiliation":[{"name":"6Monash Haematology, Monash Health and Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4250-4448","authenticated-orcid":false,"given":"Lynette","family":"Chee","sequence":"additional","affiliation":[{"name":"7Department of Clinical Haematology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre and Department of Medicine, University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Viiala","sequence":"additional","affiliation":[{"name":"8Haematology Department, Liverpool Hospital and University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilona","family":"Cunningham","sequence":"additional","affiliation":[{"name":"9Haematology Department, Concord Hospital and University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7171-2935","authenticated-orcid":false,"given":"David M.","family":"Ross","sequence":"additional","affiliation":[{"name":"1Haematology Department, Royal Adelaide Hospital, Adelaide Medical School, University of Adelaide and Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia"},{"name":"10Haematology Department, Flinders Medical Centre and Flinders University, Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alwyn","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"11Haematology Department, Wellington Hospital and University of Otago, Wellington, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Wright","sequence":"additional","affiliation":[{"name":"12Haematology Department, Fiona Stanley Hospital and University of Western Australia, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Harrup","sequence":"additional","affiliation":[{"name":"13Haematology Department, Royal Hobart Hospital and University of Tasmania, Hobart, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9108-3088","authenticated-orcid":false,"given":"Cecily","family":"Forsyth","sequence":"additional","affiliation":[{"name":"14Haematology Department, Gosford Hospital, Gosford, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Filshie","sequence":"additional","affiliation":[{"name":"15Haematology Department, St Vincent\u2019s Hospital and University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8050-6209","authenticated-orcid":false,"given":"Steven","family":"Lane","sequence":"additional","affiliation":[{"name":"16Cancer Care Services, Royal Brisbane and Women's Hospital and University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Browett","sequence":"additional","affiliation":[{"name":"17Haematology Department, Auckland Hospital and University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2788-9893","authenticated-orcid":false,"given":"Carolyn","family":"Grove","sequence":"additional","affiliation":[{"name":"18Haematology Department, Sir Charles Gardiner Hospital and PathWest, University of Western Australia, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Grigg","sequence":"additional","affiliation":[{"name":"19Haematology Department, Austin Hospital and University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy P.","family":"Hughes","sequence":"additional","affiliation":[{"name":"1Haematology Department, Royal Adelaide Hospital, Adelaide Medical School, University of Adelaide and Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"10","key":"2024110716201824800_bib1","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1056\/NEJMoa1609324","article-title":"Long-term outcomes of imatinib treatment for chronic myeloid leukemia","volume":"376","author":"Hochhaus","year":"2017","journal-title":"N\u00a0Engl J Med"},{"issue":"24","key":"2024110716201824800_bib2","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1200\/JCO.2015.66.2866","article-title":"Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population","volume":"34","author":"Bower","year":"2016","journal-title":"J\u00a0Clin Oncol"},{"issue":"5","key":"2024110716201824800_bib3","doi-asserted-by":"crossref","first-page":"e186","DOI":"10.1016\/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"},{"issue":"2","key":"2024110716201824800_bib4","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","volume":"35","author":"Kantarjian","year":"2021","journal-title":"Leukemia"},{"issue":"7","key":"2024110716201824800_bib5","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":"20","key":"2024110716201824800_bib6","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-Naive Chronic Myeloid Leukemia Patients Trial","volume":"34","author":"Cortes","year":"2016","journal-title":"J\u00a0Clin Oncol"},{"issue":"19","key":"2024110716201824800_bib7","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1056\/NEJMoa1306494","article-title":"A\u00a0phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias","volume":"369","author":"Cortes","year":"2013","journal-title":"N\u00a0Engl J Med"},{"issue":"7647","key":"2024110716201824800_bib8","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/nature21702","article-title":"The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1","volume":"543","author":"Wylie","year":"2017","journal-title":"Nature"},{"issue":"6","key":"2024110716201824800_bib9","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/S0092-8674(03)00191-0","article-title":"A\u00a0myristoyl\/phosphotyrosine switch regulates c-Abl","volume":"112","author":"Hantschel","year":"2003","journal-title":"Cell"},{"key":"2024110716201824800_bib10","doi-asserted-by":"crossref","first-page":"106458","DOI":"10.1016\/j.leukres.2020.106458","article-title":"The specificity of asciminib, a potential treatment for chronic myeloid leukemia, as a myristate-pocket binding ABL inhibitor and analysis of its interactions with mutant forms of BCR-ABL1 kinase","volume":"98","author":"Manley","year":"2020","journal-title":"Leuk Res"},{"issue":"24","key":"2024110716201824800_bib11","doi-asserted-by":"crossref","first-page":"2315","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\u00a0Engl J Med"},{"issue":"21","key":"2024110716201824800_bib12","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1182\/blood.2020009984","article-title":"A\u00a0phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs","volume":"138","author":"Rea","year":"2021","journal-title":"Blood"},{"key":"2024110716201824800_bib13","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ccell.2019.08.004","article-title":"Combining the allosteric inhibitor asciminib with ponatinib suppresses emergence of and restores efficacy against highly resistant BCR-ABL1 mutants","volume":"36","author":"Eide","year":"2019","journal-title":"Cancer Cell"},{"issue":"6","key":"2024110716201824800_bib14","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1182\/blood-2013-05-501569","article-title":"European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013","volume":"122","author":"Baccarani","year":"2013","journal-title":"Blood"},{"issue":"4","key":"2024110716201824800_bib15","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":"3","key":"2024110716201824800_bib16","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1046\/j.1365-2141.1999.01749.x","article-title":"Monitoring chronic myeloid leukaemia therapy by real-time quantitative PCR in blood is a reliable alternative to bone marrow cytogenetics","volume":"107","author":"Branford","year":"1999","journal-title":"Br J Haematol"},{"issue":"11","key":"2024110716201824800_bib17","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1038\/s41375-023-02048-y","article-title":"European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia","volume":"37","author":"Cross","year":"2023","journal-title":"Leukemia"},{"issue":"10","key":"2024110716201824800_bib18","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1007\/s40262-022-01148-9","article-title":"Population pharmacokinetics of asciminib in tyrosine kinase inhibitor-treated patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic and acute phases","volume":"61","author":"Li","year":"2022","journal-title":"Clin Pharmacokinet"},{"issue":"5","key":"2024110716201824800_bib19","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1002\/cpt.2699","article-title":"Exposure\u2013efficacy analysis of asciminib in Philadelphia chromosome\u2013positive chronic myeloid leukemia in chronic phase","volume":"112","author":"Combes","year":"2022","journal-title":"Clin Pharmacol Ther"},{"key":"2024110716201824800_bib20","author":"Jennison","year":"1999"},{"issue":"1","key":"2024110716201824800_bib21","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1001\/jamaoncol.2020.5774","article-title":"Assessment of outcomes after stopping tyrosine kinase inhibitors among patients with chronic myeloid leukemia: a nonrandomized clinical trial","volume":"7","author":"Atallah","year":"2021","journal-title":"JAMA Oncol"},{"issue":"4","key":"2024110716201824800_bib22","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1182\/blood-2014-03-566323","article-title":"Prognosis for patients with CML and &gt;10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline","volume":"124","author":"Branford","year":"2014","journal-title":"Blood"},{"issue":"1","key":"2024110716201824800_bib23","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1182\/asheducation-2014.1.240","article-title":"Prognostic significance of early molecular response in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors","volume":"2014","author":"Yeung","year":"2014","journal-title":"Hematology Am Soc Hematol Educ Program"},{"issue":"4","key":"2024110716201824800_bib24","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1182\/blood-2013-06-511592","article-title":"Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION)","volume":"123","author":"Jabbour","year":"2014","journal-title":"Blood"},{"issue":"1","key":"2024110716201824800_bib25","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/bjh.13108","article-title":"Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia: results from the 24-month follow-up of the BELA trial","volume":"168","author":"Brummendorf","year":"2015","journal-title":"Br J Haematol"},{"issue":"9","key":"2024110716201824800_bib26","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1182\/blood-2013-06-510396","article-title":"Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib","volume":"123","author":"Hughes","year":"2014","journal-title":"Blood"},{"issue":"2","key":"2024110716201824800_bib27","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/bjh.16381","article-title":"Long-term data from a phase 3 study of radotinib versus imatinib in patients with newly diagnosed, chronic myeloid leukaemia in the chronic phase (RERISE)","volume":"189","author":"Do","year":"2020","journal-title":"Br J Haematol"},{"issue":"5","key":"2024110716201824800_bib28","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/S1470-2045(16)00080-2","article-title":"Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial","volume":"17","author":"Lipton","year":"2016","journal-title":"Lancet Oncol"},{"issue":"17 suppl","key":"2024110716201824800_bib29","article-title":"ASC4FIRST, a pivotal phase 3 study of asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS TKIs) in newly diagnosed patients (pts) with chronic myeloid leukemia (CML): primary results [abstract]","volume":"42","author":"Hughes","year":"2024","journal-title":"J\u00a0Clin Oncol"}],"updated-by":[{"DOI":"10.1182\/blood.2025031951","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000}}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/144\/19\/1993\/2312132\/blood_bld-2024-024657-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/144\/19\/1993\/2312132\/blood_bld-2024-024657-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T11:20:30Z","timestamp":1730978430000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/144\/19\/1993\/517275\/Asciminib-monotherapy-as-frontline-treatment-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,7]]},"references-count":29,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2024,11,7]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2024024657","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,7]]}}}