{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:10:36Z","timestamp":1793945436420,"version":"4.8.0"},"reference-count":47,"publisher":"American Society of Hematology","issue":"13","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3,26]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Many patients receiving frontline tyrosine kinase inhibitors (TKIs) for chronic-phase chronic myeloid leukemia (CML-CP) experience inadequate disease control and\/or adverse events (AEs) that impair quality of life. Treatments offering optimal efficacy, safety, and tolerability will support long-term therapy. In the primary analysis from the ASC4FIRST trial, a phase 3 randomized trial comparing asciminib with investigator-selected TKIs (IS-TKIs) in newly diagnosed CML-CP, asciminib demonstrated superior efficacy vs all IS-TKIs and vs imatinib in the imatinib stratum, meeting both primary objectives. In the secondary analysis (2.2 years' median follow-up), major molecular response (MMR) rate at week 96 was 74.1% with asciminib vs 52.0% with IS-TKIs (treatment difference, 22.4% [95% confidence interval (CI), 13.6-31.3]; 1-sided P&amp;lt; .001) and 76.2% with asciminib vs 47.1% with imatinib in the imatinib stratum (treatment difference, 29.7% [95% CI, 17.6-41.8]; 1-sided P&amp;lt; .001), meeting both key secondary objectives. MMR rate was 72.0% with asciminib vs 56.9% with second-generation (2G) TKIs (treatment difference, 15.1% [95% CI, 2.3-28.0]; 1-sided P&amp;lt; .05), suggesting possible clinical benefit, although the study was not designed to formally confirm statistical significance for this secondary end point. Safety\/tolerability remained favorable with asciminib vs IS-TKIs. Dose reductions and interruptions, respectively, occurred with asciminib (18.5%; 46.5%), imatinib (23.2%; 47.5%), and 2G TKIs (54.9%; 63.7%). The hazard ratio for time to discontinuation of treatment due to AEs for asciminib vs 2G TKIs was 0.46 (95% CI, 0.215-0.997). With longer follow-up, asciminib continued to demonstrate a favorable benefit-risk profile over IS-TKIs and imatinib, supporting its potential as a treatment option for newly diagnosed CML-CP. This trial was registered at www.clinicaltrials.gov as NCT04971226.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025029210","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T22:10:47Z","timestamp":1765836647000},"page":"1433-1446","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":20,"title":["Asciminib demonstrates superior efficacy and safety in newly diagnosed chronic myeloid leukemia in the ASC4FIRST trial"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-1071","authenticated-orcid":false,"given":"Jorge E.","family":"Cortes","sequence":"first","affiliation":[{"name":"1Department of Medicine, Georgia Cancer Center at Augusta University, Augusta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0910-3730","authenticated-orcid":false,"given":"Timothy 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Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2640-4911","authenticated-orcid":false,"given":"Dennis Dong Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"5Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0567-9887","authenticated-orcid":false,"given":"Jiri","family":"Mayer","sequence":"additional","affiliation":[{"name":"6Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-0997","authenticated-orcid":false,"given":"Yeow-Tee","family":"Goh","sequence":"additional","affiliation":[{"name":"7Department of Hematology, Singapore General Hospital, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"le Coutre","sequence":"additional","affiliation":[{"name":"8Department of Oncology and Hematology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7600-4954","authenticated-orcid":false,"given":"Gabriel","family":"Etienne","sequence":"additional","affiliation":[{"name":"9Hematology Department, Institut Bergoni\u00e9, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inho","family":"Kim","sequence":"additional","affiliation":[{"name":"10Department of Internal Medicine, Seoul National University Hospital, Biomedical Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of 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