{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:47:11Z","timestamp":1779889631789,"version":"3.53.1"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100023368","name":"Eisai Co., Ltd.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100023368","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":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Previously, we reported the efficacy and safety of tazemetostat in Japanese patients with relapsed\/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) harboring the <jats:italic>EZH2<\/jats:italic> mutation in a multicenter, open-label, phase II study. Here, we present a follow-up analysis of tazemetostat at a long-term median follow-up of 35.0\u00a0months. Twenty patients were enrolled: 17 in the FL cohort and three in the DLBCL cohort. In the FL cohort, the objective response rate was 70.6%, consistent with the primary analysis, and the median progression-free survival (PFS) was not reached. The 24-month and 36-month PFS rates were 72.1% (95% confidence interval [CI] 41.5%\u201388.6%) and 64.1% (95% CI 33.7%\u201383.4%), respectively. The median duration of treatment was 30.2\u00a0months. After the primary analysis at a median follow-up of 12.9\u00a0months, grade 1\u20132 urinary tract infection, peripheral motor neuropathy, and hypogammaglobulinemia newly emerged, but the incidence of adverse events (AEs) did not increase notably during this follow-up period. No unexpected grade\u2009\u2265\u20093 treatment-related AEs were reported. Long-term oral monotherapy with tazemetostat showed favorable efficacy and safety profiles, indicating that it may be a useful third-line or later treatment option for patients with relapsed\/refractory FL harboring the <jats:italic>EZH2<\/jats:italic> mutation. <jats:italic>Trial registration:<\/jats:italic> ClinicalTrials.gov: NCT03456726.<\/jats:p>","DOI":"10.1007\/s12185-024-03834-9","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T18:03:34Z","timestamp":1724436214000},"page":"621-630","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Tazemetostat for relapsed\/refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan: 3-year follow-up for a phase II study"],"prefix":"10.1007","volume":"120","clinical-trial-number":[{"clinical-trial-number":"nct03456726","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-8057","authenticated-orcid":false,"given":"Koji","family":"Izutsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Ando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momoko","family":"Nishikori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohiko","family":"Shibayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Goto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Kuroda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Imaizumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kisato","family":"Nosaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maho","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichiro","family":"Hojo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Rai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"3834_CR1","doi-asserted-by":"publisher","first-page":"7922","DOI":"10.1073\/pnas.1303800110","volume":"110","author":"SK Knutson","year":"2013","unstructured":"Knutson SK, Warholic NM, Wigle TJ, Klaus CR, Allain CJ, Raimondi A, et al. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc Natl Acad Sci USA. 2013;110:7922\u20137.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3834_CR2","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1158\/1535-7163.MCT-13-0773","volume":"13","author":"SK Knutson","year":"2014","unstructured":"Knutson SK, Kawano S, Minoshima Y, Warholic NM, Huang KC, Xiao Y, et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma. Mol Cancer Ther. 2014;13:842\u201354.","journal-title":"Mol Cancer Ther"},{"key":"3834_CR3","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1016\/S1470-2045(20)30441-1","volume":"21","author":"F Morschhauser","year":"2020","unstructured":"Morschhauser F, Tilly H, Chaidos A, McKay P, Phillips T, Assouline S, et al. Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial. Lancet Oncol. 2020;21:1433\u201342.","journal-title":"Lancet Oncol"},{"key":"3834_CR4","doi-asserted-by":"publisher","first-page":"3627","DOI":"10.1111\/cas.15040","volume":"112","author":"K Izutsu","year":"2021","unstructured":"Izutsu K, Ando K, Nishikori M, Shibayama H, Teshima T, Kuroda J, et al. Phase II study of tazemetostat for relapsed or refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan. Cancer Sci. 2021;112:3627\u201335.","journal-title":"Cancer Sci"},{"key":"3834_CR5","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/S1470-2045(18)30145-1","volume":"19","author":"A Italiano","year":"2018","unstructured":"Italiano A, Soria JC, Toulmonde M, Michot JM, Lucchesi C, Varga A, et al. Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study. Lancet Oncol. 2018;19:649\u201359.","journal-title":"Lancet Oncol"},{"key":"3834_CR6","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41408-020-00340-z","volume":"10","author":"CL Batlevi","year":"2020","unstructured":"Batlevi CL, Sha F, Alperovich A, Ni A, Smith K, Ying Z, et al. Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups. Blood Cancer J. 2020;10:74.","journal-title":"Blood Cancer J"},{"key":"3834_CR7","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1200\/JCO.19.00010","volume":"37","author":"JP Leonard","year":"2019","unstructured":"Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, et al. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019;37:1188\u201399.","journal-title":"J Clin Oncol"},{"key":"3834_CR8","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/cncr.24714","volume":"116","author":"BS Kahl","year":"2010","unstructured":"Kahl BS, Bartlett NL, Leonard JP, Chen L, Ganjoo K, Williams ME, et al. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma. Cancer. 2010;116:106\u201314.","journal-title":"Cancer"},{"key":"3834_CR9","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/B978-0-323-91367-6.00011-8","volume-title":"Epigenetic cancer therapy","author":"S Kim","year":"2023","unstructured":"Kim S, Barkey N, Atasoylu O, Dhanak D. Chapter 16 - epigenetic therapies\u2014update on lysine methyltransferase\/PRC complex inhibitors. In: Gray SG, editor. Epigenetic cancer therapy. 2nd ed. Boston: Academic Press; 2023. p. 373\u2013405.","edition":"2"}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-024-03834-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-024-03834-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-024-03834-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T08:44:48Z","timestamp":1730105088000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-024-03834-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,23]]},"references-count":9,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["3834"],"URL":"https:\/\/doi.org\/10.1007\/s12185-024-03834-9","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,23]]},"assertion":[{"value":"27 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 July 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 August 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":"Koji Izutsu received research funding from Eisai Co., Ltd., related to the submitted work; received research funding from Chugai Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., Incyte Biosciences Japan G.K., Genmab K.K., Loxo Oncology, Inc., Daiichi Sankyo Co., Ltd., BeiGene, Inc., AbbVie G.K., AstraZeneca K.K., Regeneron Pharmaceuticals, Inc., Yakult Honsha Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Novartis Pharma K.K., Pfizer Inc., MSD K.K., Bayer Yakuhin, Ltd., Kyowa Kirin Co., Ltd., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Ltd., Gilead Sciences, Inc., and Amgen Astellas BioPharma K.K.; consulting fees from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corp., Eisai Co., Ltd., Chugai Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., AbbVie G.K., Takeda Pharmaceutical Co., Ltd., Zenyaku Holdings Co., Ltd., Genmab K.K., Kyowa Kirin Co., Ltd., MSD K.K., Carna Biosciences, Inc., Novartis Pharma K.K., Yakult Honsha Co., Ltd., Nippon Shinyaku Co., Ltd., and BeiGene, Inc.; honoraria from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., SymBio Pharmaceuticals Ltd., Bristol-Myers Squibb K.K., Daiichi Sankyo Co., Ltd., Otsuka Pharmaceutical Co., Ltd., AbbVie G.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Genmab K.K., Kyowa Kirin Co., Ltd., MSD K.K., Astellas Pharma Inc., Pfizer Inc., Meiji Seika Pharma Co., Ltd., Novartis Pharma K.K., Nippon Kayaku Co., Ltd., and Gilead Sciences, Inc., outside the submitted work. Kiyoshi Ando received research funding from Eisai Co., Ltd., related to the submitted work; received research funding from Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Nippon Shinyaku Co., Ltd., Novartis Pharma K.K., Astellas Pharma Inc., Asahi Kasei Pharma Corp., and Otsuka Pharmaceutical Co., Ltd.; honoraria from Janssen Pharmaceutical K.K., Bristol-Myers Squibb K.K., Ono Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., and Eisai Co., Ltd., outside the submitted work. Momoko Nishikori received research funding from Eisai Co., Ltd., related to the submitted work; received research funding from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., and SymBio Pharmaceuticals Ltd.; honoraria from Novartis Pharma K.K., AbbVie G.K., Bristol-Myers Squibb K.K., Gilead Sciences, Inc., Genmab K.K., SymBio Pharmaceuticals Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., AstraZeneca K.K., Sumitomo Pharma Co., Ltd., Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Eisai Co., Ltd., and Kyowa Kirin Co., Ltd., outside the submitted work. Hirohiko Shibayama received research funding from Eisai Co., Ltd., related to the submitted work; received research funding from Bristol-Myers Squibb K.K., Ono Pharmaceutical Co., Ltd., and AbbVie G.K.; honoraria from Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Sanofi K.K., Fujimoto Pharmaceutical Corporation, Meiji Seika Pharma Co., Ltd., and Nippon Shinyaku Co., Ltd.; is an\u00a0advisory board member of Chugai Pharmaceutical Co., Ltd., AbbVie G.K., Ono Pharmaceutical Co., Ltd., and Janssen Pharmaceutical K.K., outside the submitted work; and\u00a0is an editorial board member of International Journal of Hematology. Hirohiko Shibayama is the editor of International Journal of Hematology. Hideki Goto received honoraria from Novartis Pharma K.K., Kyowa Kirin Co., Ltd., and Chugai Pharmaceutical Co., Ltd.; payment for expert testimony from Sanofi K.K., SymBio Pharmaceuticals Ltd., Bristol-Myers Squibb K.K., and Kyowa Kirin Co., Ltd., outside the submitted work. Junya Kuroda received research funding from Eisai Co., Ltd., related to the submitted work; received research funding from Kyowa Kirin Co., Ltd., Chugai Pharmaceutical Co., Ltd., Asahi Kasei Pharma Corp., Sumitomo Pharma Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., and Japan Blood Products Organization; consulting fees from Bristol-Myers Squibb K.K., Janssen Pharmaceutical K.K., Pfizer Inc., AbbVie G.K., and BeiGene, Inc.; honoraria from Bristol-Myers Squibb K.K., Janssen Pharmaceutical K.K., Sanofi K.K., Kyowa Kirin Co., Ltd., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., AstraZeneca K.K., Astellas Pharma Inc., Eisai Co., Ltd., AbbVie G.K., Novartis Pharma K.K., Daiichi Sankyo Co., Ltd., Amgen K.K., and Otsuka Pharmaceutical Co., Ltd., outside the submitted work. Koji Kato received research funding from Eisai Co., Ltd., related to the submitted work; received research funding from Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., AbbVie G.K., Novartis Pharma K.K., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Celgene K.K., Ono Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd, Daiichi Sankyo Co., Ltd., MSD K.K., Bristol-Myers Squibb K.K., Gilead Sciences, Inc., and Astellas Pharma Inc.; honoraria from Novartis Pharma K.K., Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., and Meiji Seika Pharma Co., Ltd., outside the submitted work. Yoshitaka Imaizumi received honoraria from Kyowa Kirin Co., Ltd., Daiichi Sankyo Co., Ltd., SymBio Pharmaceuticals Ltd., Sanofi K.K., Bristol-Myers Squibb K.K., Meiji Seika Pharma Co., Ltd., AstraZeneca K.K., and Chugai Pharmaceutical Co., Ltd., outside the submitted work. Kisato Nosaka received research funding from Kyowa Kirin Co., Ltd. and Chugai Pharmaceutical Co., Ltd.; honoraria from Meiji Seika Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., Kyowa Kirin Co., Ltd., AbbVie G.K., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Ohara Pharmaceutical Co., Ltd., and Janssen Pharmaceutical K.K., outside the submitted work. Rika Sakai received research funding from Eisai Co., Ltd., related to the submitted work; research funding from Kyowa Kirin Co., Ltd., Chugai Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd.; honoraria from Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., AstraZeneca K.K., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., CSL Behring K.K., Eisai Co., Ltd., Nippon Shinyaku Co., Ltd., Bristol-Myers Squibb K.K., Mundipharma K.K., Nihon Medi-Physics Co., Ltd., Chugai Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., Sanofi K.K., Towa Pharmaceutical Co., Ltd., Sekisui Medical Co., Ltd., and Daiichi Sankyo Co., Ltd., outside the submitted work. Maho Abe, Seiichiro Hojo, and Tadashi Nakanishi are employees of Eisai Co., Ltd. Shinya Rai had no conflict of interest to be declared.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}