{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T13:02:10Z","timestamp":1776258130254,"version":"3.50.1"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100011725","name":"Servier","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ivosidenib is a mutant IDH1 (mIDH1) inhibitor that demonstrated clinical benefit in combination with azacitidine for treatment of m\n                    <jats:italic>IDH1<\/jats:italic>\n                    acute myeloid leukemia (AML) in the phase 3 AGILE trial. Results from AGILE led to the approval of ivosidenib plus azacitidine for patients with newly diagnosed m\n                    <jats:italic>IDH1<\/jats:italic>\n                    AML unfit for intensive chemotherapy in Japan. However, data on the use of ivosidenib plus azacitidine in Japanese patients with m\n                    <jats:italic>IDH1<\/jats:italic>\n                    AML are lacking. Here we present data from six Japanese patients enrolled in AGILE, of whom, three received ivosidenib plus azacitidine and three received placebo plus azacitidine. At data cut-off, Japanese patients in AGILE had an overall survival of 4.4\u201312.8\u00a0months and 24.8\u201336.5\u00a0months in the placebo plus azacitidine and ivosidenib plus azacitidine groups, respectively. Of the Japanese patients enrolled in AGILE, 2 of 3 (66.7%) patients receiving ivosidenib plus azacitidine and none receiving placebo plus azacitidine achieved complete remission within 24\u00a0weeks. Results from the Japanese population enrolled in AGILE are aligned with those of the overall study. The efficacy of ivosidenib plus azacitidine in Japanese m\n                    <jats:italic>IDH1<\/jats:italic>\n                    AML patients enrolled in AGILE who were ineligible for intensive chemotherapy appears to be consistent with the overall study population.\n                  <\/jats:p>","DOI":"10.1007\/s12185-026-04175-5","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T05:48:39Z","timestamp":1772516919000},"page":"509-515","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A narrative review of mutant isocitrate dehydrogenase AML in Japan based on experience with ivosidenib in AGILE"],"prefix":"10.1007","volume":"123","author":[{"given":"Yasushi","family":"Hiramatsu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Urata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Yamauchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"4175_CR1","unstructured":"Foundation for Promotion of Cancer Research. Cancer Statistics In Japan 2016 [Available from: https :\/\/ganjo ho.jp\/data\/reg_stat\/stati stics \/brochure\/2016\/cance r_stati stics 2016_fig_J.pdf."},{"issue":"1","key":"4175_CR2","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1007\/s12185-023-03677-w","volume":"119","author":"K Usuki","year":"2024","unstructured":"Usuki K, Ohtake S, Honda S, Matsuda M, Wakita A, Nawa Y, et al. Real-world data of AML in Japan: results of JALSG clinical observational study-11 (JALSG-CS-11). Int J Hematol. 2024;119(1):24\u201338.","journal-title":"Int J Hematol"},{"issue":"4","key":"4175_CR3","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1007\/s12185-024-03730-2","volume":"119","author":"Y Maeda","year":"2024","unstructured":"Maeda Y. JSH practical guidelines for hematological malignancies, 2023: I. Leukemia-1. Acute myeloid leukemia (AML). Int J Hematol. 2024;119(4):347\u201373.","journal-title":"Int J Hematol"},{"issue":"6","key":"4175_CR4","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1007\/s10147-025-02758-6","volume":"30","author":"N Matsumura","year":"2025","unstructured":"Matsumura N, Mandai M. PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs; approval of amivantamab plus lazertinib for non-small cell lung cancer, durvalumab for small cell lung cancer, tislelizumab for esophageal cancer, tisotumab vedotin for cervical cancer, ivosidenib for leukemia, and venetoclax for lymphoma in Japan. Int J Clin Oncol. 2025;30(6):1049\u201350.","journal-title":"Int J Clin Oncol"},{"issue":"6","key":"4175_CR5","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000583","volume":"5","author":"BJ Wouters","year":"2021","unstructured":"Wouters BJ. Targeting IDH1 and IDH2 mutations in acute myeloid leukemia: emerging options and pending questions. Hemasphere. 2021;5(6):e583.","journal-title":"Hemasphere"},{"issue":"1","key":"4175_CR6","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1309\/AJCPD7NR2RMNQDVF","volume":"135","author":"KP Patel","year":"2011","unstructured":"Patel KP, Ravandi F, Ma D, Paladugu A, Barkoh BA, Medeiros LJ, et al. Acute myeloid leukemia with IDH1 or IDH2 mutation: frequency and clinicopathologic features. Am J Clin Pathol. 2011;135(1):35\u201345.","journal-title":"Am J Clin Pathol"},{"issue":"4","key":"4175_CR7","first-page":"254","volume":"2","author":"JH Feng","year":"2012","unstructured":"Feng JH, Guo XP, Chen YY, Wang ZJ, Cheng YP, Tang YM. Prognostic significance of IDH1 mutations in acute myeloid leukemia: a meta-analysis. Am J Blood Res. 2012;2(4):254\u201364.","journal-title":"Am J Blood Res"},{"issue":"16","key":"4175_CR8","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1056\/NEJMoa2117344","volume":"386","author":"P Montesinos","year":"2022","unstructured":"Montesinos P, Recher C, Vives S, Zarzycka E, Wang J, Bertani G, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N Engl J Med. 2022;386(16):1519\u201331.","journal-title":"N Engl J Med"},{"issue":"20","key":"4175_CR9","doi-asserted-by":"publisher","first-page":"5177","DOI":"10.1182\/bloodadvances.2025016399","volume":"9","author":"P Montesinos","year":"2025","unstructured":"Montesinos P, Marchione DM, Recher C, Heuser M, Vives S, Zarzycka E, et al. Long-term results from the AGILE study of azacitidine plus ivosidenib vs placebo in newly diagnosed IDH1-mutated AML. Blood Adv. 2025;9(20):5177\u201389.","journal-title":"Blood Adv"},{"key":"4175_CR10","unstructured":"US Food & Drug Administration. FDA approves ivosidenib in combination with azacitidine for newly diagnosed acute myeloid leukemia 2022 [Available from: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-ivosidenib-combination-azacitidine-newly-diagnosed-acute-myeloid-leukemia."},{"key":"4175_CR11","unstructured":"European Medicines Agency. Tibsovo - ivosidenib 2023 [Available from: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/tibsovo]."},{"key":"4175_CR12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-149801","volume":"138","author":"S Uchiyama","year":"2021","unstructured":"Uchiyama S, Hirotaka N, Chi SG, Fukushima K, Shibayama H, Hosono N, et al. Properties and distribution of IDH-1\/2 mutations in acute myeloid leukemia by the comprehensive genomic analysis. Blood. 2021;138:4447.","journal-title":"Blood"},{"issue":"9","key":"4175_CR13","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1093\/jjco\/hyab112","volume":"51","author":"T Yamauchi","year":"2021","unstructured":"Yamauchi T, Yoshida C, Usuki K, Takada S, Matsumura I, Dobashi N, et al. Venetoclax plus low-dose cytarabine in Japanese patients with untreated acute myeloid leukaemia ineligible for intensive chemotherapy. Jpn J Clin Oncol. 2021;51(9):1372\u201382.","journal-title":"Jpn J Clin Oncol"},{"issue":"1","key":"4175_CR14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/jjco\/hyab170","volume":"52","author":"K Yamamoto","year":"2022","unstructured":"Yamamoto K, Shinagawa A, DiNardo CD, Pratz KW, Ishizawa K, Miyamoto T, et al. Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Jpn J Clin Oncol. 2022;52(1):29\u201338.","journal-title":"Jpn J Clin Oncol"},{"issue":"6","key":"4175_CR15","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1111\/ejh.12271","volume":"92","author":"S Yamaguchi","year":"2014","unstructured":"Yamaguchi S, Iwanaga E, Tokunaga K, Nanri T, Shimomura T, Suzushima H, et al. IDH1 and IDH2 mutations confer an adverse effect in patients with acute myeloid leukemia lacking the NPM1 mutation. Eur J Haematol. 2014;92(6):471\u20137.","journal-title":"Eur J Haematol"},{"issue":"19","key":"4175_CR16","doi-asserted-by":"publisher","first-page":"5941","DOI":"10.1182\/bloodadvances.2022008282","volume":"7","author":"S Zarnegar-Lumley","year":"2023","unstructured":"Zarnegar-Lumley S, Alonzo TA, Gerbing RB, Othus M, Sun Z, Ries RE, et al. Characteristics and prognostic impact of IDH mutations in AML: a COG, SWOG, and ECOG analysis. Blood Adv. 2023;7(19):5941\u201353.","journal-title":"Blood Adv"},{"issue":"4","key":"4175_CR17","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1111\/bjh.12659","volume":"164","author":"D Chihara","year":"2014","unstructured":"Chihara D, Ito H, Matsuda T, Shibata A, Katsumi A, Nakamura S, et al. Differences in incidence and trends of haematological malignancies in Japan and the United States. Br J Haematol. 2014;164(4):536\u201345.","journal-title":"Br J Haematol"},{"issue":"5","key":"4175_CR18","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1111\/cas.15746","volume":"114","author":"N Hosono","year":"2023","unstructured":"Hosono N, Chi S, Yamauchi T, Fukushima K, Shibayama H, Katagiri S, et al. Clinical utility of genomic profiling of AML using paraffin-embedded bone marrow clots: HM-SCREEN-Japan 01. Cancer Sci. 2023;114(5):2098\u2013108.","journal-title":"Cancer Sci"},{"key":"4175_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-4-46","volume":"4","author":"G Wei","year":"2011","unstructured":"Wei G, Ni W, Chiao JW, Cai Z, Huang H, Liu D. A meta-analysis of CAG (cytarabine, aclarubicin, G-CSF) regimen for the treatment of 1029 patients with acute myeloid leukemia and myelodysplastic syndrome. J Hematol Oncol. 2011;4:46.","journal-title":"J Hematol Oncol"},{"key":"4175_CR20","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.leukres.2015.12.013","volume":"42","author":"D Minakata","year":"2016","unstructured":"Minakata D, Fujiwara S, Ito S, Mashima K, Umino K, Nakano H, et al. A low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor priming regimen versus a daunorubicin plus cytarabine regimen as induction therapy for older patients with acute myeloid leukemia: a propensity score analysis. Leuk Res. 2016;42:82\u20137.","journal-title":"Leuk Res"},{"issue":"3","key":"4175_CR21","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1182\/blood-2015-01-621664","volume":"126","author":"H Dombret","year":"2015","unstructured":"Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126(3):291\u20139.","journal-title":"Blood"},{"issue":"1","key":"4175_CR22","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s12185-022-03334-8","volume":"116","author":"C Yoshida","year":"2022","unstructured":"Yoshida C, Kondo T, Ito T, Kizaki M, Yamamoto K, Miyamoto T, et al. Real-world treatment patterns and clinical outcomes in patients with AML in Japan who were ineligible for first-line intensive chemotherapy. Int J Hematol. 2022;116(1):89\u2013101.","journal-title":"Int J Hematol"},{"issue":"7","key":"4175_CR23","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1056\/NEJMoa2012971","volume":"383","author":"CD DiNardo","year":"2020","unstructured":"DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617\u201329.","journal-title":"N Engl J Med"}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-026-04175-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-026-04175-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-026-04175-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T11:56:39Z","timestamp":1776254199000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-026-04175-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,3]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["4175"],"URL":"https:\/\/doi.org\/10.1007\/s12185-026-04175-5","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,3]]},"assertion":[{"value":"14 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Yasushi Hiramatsu: payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Nihon Servier. Shingo Urata: support for attending meetings and\/or travel, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Nihon Servier. Takayuki Ishikawa: no conflicts of interest to declare. Takahiro Yamauchi: grants or contracts from Servier; consulting fees from Servier, AbbVie, and Nippon Shinyaku; payment for expert testimonies from Otsuka Pharmaceutical and Ohara Pharmaceutical; and receipt of equipment, materials, drugs, medical writing, gifts or other services from Jazz Pharmaceuticals, Pfizer, and Nippon Kayaku.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}