Asciminib remained superior vs bosutinib in late-line CML-CP after nearly 4 years of follow-up in ASCEMBL.

Philipp le Coutre, Vishal Dhamal, Noemi Espurz, Shruti Kapoor, Timothy P Hughes, Andreas Hochhaus, Jorge E Cortes, Valentin García-Gutiérrez, Lynette Chee, Koji Sasaki, Naeem Chaudhri, Mario Annunziata, Susanne Saussele, Delphine Rea, Dennis Dong Hwan Kim, Laura Maria Fogliatto, Andre Abdo, Jane F Apperley, Dong-Wook Kim, Anna Turkina, Sergey Voloshin, Elza Lomaia, Yosuke Minami, Carla Boquimpani, Michael J Mauro

Journal: Blood advances 2025;9(16):4248-4259

PMID: 40334072

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Abstract

The efficacy of and disease control afforded by tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia in chronic phase (CML-CP) have led to increased longevity and thus the continued pursuit of alternative therapies that are efficacious and maximize tolerability. The 24- and 96-week analyses from ASCEMBL demonstrated superior efficacy, safety, and tolerability of asciminib when compared with bosutinib in later-line therapy, thereby meeting the primary and key secondary objectives. With nearly 4 years of follow-up, data from ASCEMBL continued to demonstrate the superior efficacy, safety, and tolerability of asciminib over bosutinib. At week 156, the major molecular response (MMR) rates remained higher with asciminib (33.8%) than with bosutinib (10.5%); the difference in MMR rates between arms, after adjusting for baseline major cytogenetic response, was 23.2% (95% confidence interval, 13.14-33.18; 2-sided P < .001). Asciminib continued to cause fewer grade ≥3 adverse events (AEs; 59.6% vs 68.4%) and fewer AEs that led to treatment discontinuation (8.3% vs 27.6%) than bosutinib. This updated analysis also includes patients who switched to asciminib because of a lack of efficacy with bosutinib. Two of the 25 patients who switched achieved MMR by the end of study, suggesting that earlier incorporation of asciminib, before other TKIs, may improve responses, albeit modestly. These long-term results further solidify asciminib as the therapy of choice for patients with CML-CP who were previously treated with ≥2 previous TKIs. This trial was registered at clinicaltrials.gov as #NCT03106779.

© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Address: Chronic Myeloid Leukemia Program, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Hematology, National Cancer Center Hospital East, Kashiwa, Japan.; Department of Hematology and Internal Oncology, Universitätsklinikum Jena, Jena, Germany.; Institute of Oncology and Hematology, Almazov National Medical Research Centre, St Petersburg, Russia.; Hematology and Bone Marrow Transplantation, Russian Research Institute of Hematology and Transfusiology, St Petersburg, Russia.; Scientific and Advisory Department of Hemotherapy of Myeloproliferative Disorders, National Medical Research Center for Hematology, Moscow, Russia.; Hematologic Tumor Medicine Department, Uijeongbu Eulji Medical Center, Uijeongbu, South Korea.; Department of Immunology and Inflammation, Centre for Haematology, Imperial College London, London, United Kingdom.; Department of Leukemia, Georgia Cancer Center, Augusta, GA.; Hemato-Oncology Department, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil.; Hematology and Hemotherapy Department, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.; Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.; Department of Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany.; Department of Haematology and Oncology, III. Medizinische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.; Division of Hematology, Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli, Naples, Italy.; Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute and The University of Adelaide, Adelaide, SA, Australia.; Hematology, Stem Cell Transplant and Cellular Therapy Section, King Faisal Specialist Hospital & Research Centre, Riyadh, Kingdom of Saudi Arabia.; Department of Clinical Haematology, Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, VIC, Australia.; Department of Hematology and Hemotherapy, Servicio de Hematología, Hospital Universitario Ramón y Cajal, Madrid, Spain.; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.; Hematology Department, Instituto Estadual de Hematologia Arthur Siqueira Cavalcanti, Rio de Janeiro, Brazil.; Novartis Pharmaceuticals Corporation, East Hanover, NJ.; Novartis Pharma AG, Basel, Switzerland.; Novartis Healthcare Private Limited, Hyderabad, India.; DMU Hématologie, Hôpital Saint-Louis, Paris, France.

DOI: 10.1182/bloodadvances.2025016042

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MeSH Terms: Adult, Aged, Female, Humans, Male, Middle Aged, Aniline Compounds, Antineoplastic Agents, Follow-Up Studies, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Chronic-Phase, Nitriles, Protein Kinase Inhibitors, Pyrazoles, Quinolines, Treatment Outcome, Niacinamide