{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:05:24Z","timestamp":1789049124354,"version":"build-2803163510"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100030831","name":"Novartis Pharma K.K.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100030831","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Asciminib is a first-in-class BCR::ABL1 inhibitor that Specifically Targets the ABL1 Myristoyl Pocket (STAMP). It is approved worldwide and in Japan for chronic myeloid leukemia in chronic phase (CML-CP) with resistance or intolerance to previous tyrosine kinase inhibitor (TKI) therapy. In the Phase 3 ASCEMBL study, patients with CML-CP who received\u2009\u2265\u20092 prior ATP-competitive TKIs were randomized (2:1) to asciminib 40\u00a0mg twice-daily or bosutinib 500\u00a0mg once-daily. Here, we report the 96-week results of the subgroup analysis of Japanese patients (asciminib, <jats:italic>n<\/jats:italic>\u2009=\u200913; bosutinib, <jats:italic>n<\/jats:italic>\u2009=\u20093) in the ASCEMBL study. The MMR rate at Week 96 was 46.2% in asciminib-treated patients, increasing from Weeks 24 and 48. Patients who achieved MMR at Week 24 remained in MMR up to the Week 96 cutoff. While a high proportion of patients treated with asciminib remained on treatment at cutoff, none randomized to bosutinib were on treatment at Week 96. Despite the longer duration of exposure to asciminib, its safety and tolerability continued to be favorable with no new or worsening safety findings. Overall, the efficacy and safety outcomes in the Japanese subgroup were comparable with the ASCEMBL global study population, which supports the use of asciminib in Japanese patients with previously treated CML-CP.<\/jats:p>","DOI":"10.1007\/s12185-024-03805-0","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T07:03:26Z","timestamp":1718694206000},"page":"305-313","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Asciminib in Patients With CML-CP Previously Treated With\u2009\u2265\u20092 Tyrosine Kinase Inhibitors: 96-Week Results From the Japanese Subgroup Analysis of the ASCEMBL Study"],"prefix":"10.1007","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0863-0739","authenticated-orcid":false,"given":"Yosuke","family":"Minami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Doki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Yokota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Tomita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohmei","family":"Kubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsunori","family":"Goto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Kirito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Maki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meryem Ktiouet","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itaru","family":"Matsumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"issue":"24","key":"3805_CR1","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1200\/JCO.2015.66.2866","volume":"34","author":"H Bower","year":"2016","unstructured":"Bower H, Bj\u00f6rkholm M, Dickman PW, H\u00f6glund M, Lambert PC, Andersson TM. Life Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population. J Clin Oncol. 2016;34(24):2851\u20137. https:\/\/doi.org\/10.1200\/JCO.2015.66.2866.","journal-title":"J Clin Oncol"},{"key":"3805_CR2","unstructured":"Japanese Society of Hematology. JSH Practical Guidelines for Hematological Malignancies, 2023: I. Leukemia-4. Chronic myeloid leukemia (CML)\/myeloproliferative neoplasms (MPN)."},{"issue":"5","key":"3805_CR3","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s11899-021-00653-1","volume":"16","author":"E Atallah","year":"2021","unstructured":"Atallah E, Sweet K. Treatment-free remission: the new goal in CML therapy. Curr Hematol Malig Rep. 2021;16(5):433\u20139. https:\/\/doi.org\/10.1007\/s11899-021-00653-1.","journal-title":"Curr Hematol Malig Rep"},{"issue":"1","key":"3805_CR4","first-page":"17","volume":"128","author":"TP Hughes","year":"2016","unstructured":"Hughes TP, Ross DM. Moving treatment-free remission into mainstream clinical practice in CML. Blood, The Journal of the American Society of Hematology. 2016;128(1):17\u201323.","journal-title":"Blood, The Journal of the American Society of Hematology"},{"key":"3805_CR5","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1007\/s12185-020-02964-0","volume":"112","author":"K Shimoda","year":"2020","unstructured":"Shimoda K, Takahashi N, Kirito K, Iriyama N, Kawaguchi T, Kizaki M. JSH practical guidelines for hematological malignancies, 2018: I. Leukemia-4. Chronic myeloid leukemia (CML)\/myeloproliferative neoplasms (MPN). Int J Hematol. 2020;112:268\u201391.","journal-title":"Int J Hematol"},{"key":"3805_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2020.106458","volume":"98","author":"PW Manley","year":"2020","unstructured":"Manley PW, Barys L, Cowan-Jacob SW. 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. Leuk Res. 2020;98: 106458.","journal-title":"Leuk Res"},{"key":"3805_CR7","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01040","volume-title":"Discovery of asciminib (ABL001), an allosteric inhibitor of the tyrosine kinase activity of BCR-ABL1","author":"J Schoepfer","year":"2018","unstructured":"Schoepfer J, Jahnke W, Berellini G, Buonamici S, Cotesta S, Cowan-Jacob SW, et al. Discovery of asciminib (ABL001), an allosteric inhibitor of the tyrosine kinase activity of BCR-ABL1. New York: ACS Publications; 2018."},{"key":"3805_CR8","unstructured":"U. S. Food and Drug Administration. FDA approves asciminib for Philadelphia chromosome-positive chronic myeloid leukemia. Available from: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-asciminib-philadelphia-chromosome-positive-chronic-myeloid-leukemia. Accessed May 2023."},{"issue":"21","key":"3805_CR9","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1182\/blood.2020009984","volume":"138","author":"D Rea","year":"2021","unstructured":"Rea D, Mauro MJ, Boquimpani C, Minami Y, Lomaia E, Voloshin S, et al. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs. bosutinib in CML after 2 or more prior TKIs. Blood. 2021;138(21):2031\u201341.","journal-title":"Blood"},{"issue":"Supplement 1","key":"3805_CR10","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1182\/blood-2021-152561","volume":"138","author":"MJ Mauro","year":"2021","unstructured":"Mauro MJ, Minami Y, Rea D, Hochhaus A, Lomaia E, Voloshin S, et al. Efficacy and Safety Results from Ascembl, a Multicenter, Open-Label, Phase 3 Study of Asciminib, a First-in-Class STAMP Inhibitor, Vs. Bosutinib in Patients with Chronic Myeloid Leukemia in Chronic Phase after \u22652 Prior Tyrosine Kinase Inhibitors: Update after 48 Weeks. Blood. 2021;138(Supplement 1):310.","journal-title":"Blood"},{"issue":"3","key":"3805_CR11","doi-asserted-by":"publisher","first-page":"2990","DOI":"10.1002\/cam4.5212","volume":"12","author":"J Yuda","year":"2023","unstructured":"Yuda J, Doki N, Matsuoka H, Yokota T, Tomita A, Takahashi N, et al. Asciminib vs. bosutinib in CML patients pretreated with \u2265 2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study. Cancer Med. 2023;12(3):2990\u20138.","journal-title":"Cancer Med"},{"issue":"3","key":"3805_CR12","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/s41375-023-01829-9","volume":"37","author":"A Hochhaus","year":"2023","unstructured":"Hochhaus A, R\u00e9a D, Boquimpani C, Minami Y, Cortes JE, Hughes TP, et al. Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL. Leukemia. 2023;37(3):617\u201326.","journal-title":"Leukemia"},{"issue":"5","key":"3805_CR13","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1038\/s41375-018-0055-7","volume":"32","author":"S Saussele","year":"2018","unstructured":"Saussele S, Hehlmann R, Fabarius A, Jeromin S, Proetel U, Rinaldetti S, et al. Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV. Leukemia. 2018;32(5):1222\u20138.","journal-title":"Leukemia"},{"issue":"4","key":"3805_CR14","first-page":"393","volume":"132","author":"JE Cortes","year":"2018","unstructured":"Cortes JE, Kim D-W, Pinilla-Ibarz J, le Coutre PD, Paquette R, Chuah C, et al. Ponatinib efficacy and safety in Philadelphia chromosome\u2013positive leukemia: final 5-year results of the phase 2 PACE trial. Blood, The Journal of the American Society of Hematology. 2018;132(4):393\u2013404.","journal-title":"Blood, The Journal of the American Society of Hematology"},{"issue":"5","key":"3805_CR15","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1038\/s41375-023-01888-y","volume":"37","author":"D R\u00e9a","year":"2023","unstructured":"R\u00e9a D, Boquimpani C, Mauro MJ, Minami Y, Allepuz A, Maheshwari VK, D\u2019Alessio D, Wu Y, Lawrance R, Narbutas S, Sharf G, Hochhaus A. Health-related quality of life of patients with resistant\/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial. Leukemia. 2023;37(5):1060\u20137. https:\/\/doi.org\/10.1038\/s41375-023-01888-y.","journal-title":"Leukemia"}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-024-03805-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-024-03805-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-024-03805-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T11:30:44Z","timestamp":1724931044000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-024-03805-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,18]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["3805"],"URL":"https:\/\/doi.org\/10.1007\/s12185-024-03805-0","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,18]]},"assertion":[{"value":"15 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Yosuke Minami received honoraria from Astellas Pharma Inc., Novartis, Pfizer, Daiichi-Sankyo, and BMS; received consulting fees from Takeda, CMIC, Daiichi-Sankyo and BostonGene. Hiroshi Matsuoka received honoraria for lectures from Pfizer, Japan. Takafumi Yokota received honoraria from Novartis Pharma K.K. and Otsuka Pharmaceutical Co., Ltd. Akihiro Tomita received honoraria from Chugai Pharmaceutical, Takeda Pharmaceutical and Ono Pharmaceutical, and Eisai); grants from Ono Pharmaceutical, Eisai, Kyowa Kirin, Sumitomo Pharmaceutical; Nippon Kayaku; Otsuka; Nippon Shinyaku; Mochida Pharmaceutical; Asahi Kasei; Taiho Pharmaceutical; Shionogi and Takeda Pharmaceutical. Naoto Takahashi received grants from Asahikasei, Ono and Otsuka; honoraria from Novartis, Otsuka and Pfizer. Tatsunori Goto received honoraria from Novartis, AbbVie, AstraZeneca; Astellas, Kisseo Pharmaceutical. Keita Kirito received honoraria from Pharmaessentia Japan; Takeda Pharmaceutical Company Limited and Novartis Pharma K.K. Akio Maki and Makoto Aoki are employees of Novartis Pharma K.K., Japan. Meryem Ktiouet Dawson is employee of Novartis Pharma AG, Basel, Switzerland. Itaru Matsumura received honoraria from Bristol-Meyers Squibb (Celgene), Novartis Pharmaceuticals, Otsuka Pharmaceutical Co., Ltd. Pfizer Japan Inc., Janssen Pharmaceutical K.K., Astellas Pharma Inc., Takeda Pharmaceutical Company Limited., Daiichi Sankyo Company, Limited., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca, SymBio Pharmaceuticals, AbbVie GK, and Amgen BioPharma K.K.; and grants from Ono Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Nippon Shinyaku Co., Ltd., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Shionogi & Co., Ltd. Teijin Pharma Limited, Boehringer Ingelheim, Sanofi, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited., Nihon Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited., AbbVie GK, Taiho Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Nippon Kayaku Co.,Ltd., CSL Behring, Mundipharma K.K., AYUMI Pharmaceutical Corporation, Eli Lilly Japan K.K., Actelion Pharmaceuticals Japan Ltd., Amgen BioPharma K.K. Noriko Doki and Kohmei Kubo have nothing to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}