{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T15:29:43Z","timestamp":1789831783710,"version":"4.0.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T00:00:00Z","timestamp":1716595200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T00:00:00Z","timestamp":1716595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","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":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acute graft-versus-host disease (aGvHD) is a major complication after allogeneic hematopoietic stem cell transplantation in Japan and other countries. Nearly one-third of patients do not respond to standard systemic steroid therapy and no standard second-line treatment has been established in Japan. We report efficacy and safety findings of ruxolitinib versus best available therapy (BAT) from a subgroup analysis of the international, phase 3 REACH2 study in Japanese patients with steroid-refractory aGvHD. The primary endpoint was overall response rate (ORR) at day 28. Overall, 9 patients received ruxolitinib and 21 received BAT. The ORR at day 28 (88.9% vs 52.4%) and durable ORR at day 56 (66.7% vs 28.6%) were higher with ruxolitinib versus BAT. The estimated cumulative incidence of loss of response at 6\u00a0months was 12.5% with ruxolitinib and 18.2% with BAT. The median failure-free survival was longer with ruxolitinib versus BAT (2.73 vs 1.25\u00a0months). The most common adverse events up to day 28 in the ruxolitinib and BAT groups were anemia (55.6% vs 19.0%) and thrombocytopenia (44.4% vs 4.8%, respectively). Ruxolitinib showed better efficacy outcomes and a consistent safety profile compared with BAT in the Japanese subgroup, and the findings were consistent with overall study results.<\/jats:p>","DOI":"10.1007\/s12185-024-03772-6","type":"journal-article","created":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T17:01:43Z","timestamp":1716656503000},"page":"106-116","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ruxolitinib in steroid-refractory acute graft-vs-host disease: Japanese subgroup analysis of the randomized REACH2 trial"],"prefix":"10.1007","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0941-271X","authenticated-orcid":false,"given":"Takanori","family":"Teshima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Onishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Miyamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Doki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohisa","family":"Nakamae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Inamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Maki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumika","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Tajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Wroclawska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Zeiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Onizuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,25]]},"reference":[{"key":"3772_CR1","unstructured":"Hematopoietic Cell Transplantation in Japan. Annual Report of Nationwide Survey 2022 Summary Slide. 2022. The Japanese Data Center for Hematopoietic Cell Transplantation. http:\/\/www.jdchct.or.jp\/en\/data\/slide\/2022\/. Accessed 1 Aug 2023."},{"issue":"6","key":"3772_CR2","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/bmt.2016.18","volume":"51","author":"D Niederwieser","year":"2016","unstructured":"Niederwieser D, Baldomero H, Szer J, Gratwohl M, Aljurf M, Atsuta Y, et al. Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey. Bone Marrow Transplant. 2016;51(6):778\u201385.","journal-title":"Bone Marrow Transplant"},{"key":"3772_CR3","unstructured":"Japan Hematopoietic Cell Transplantation Data Center\/Japan Hematopoietic Cell Transplantation Society. Hematopoietic cell transplantation in Japan. National Survey Report. III. Analysis of transplant outcomes, Fig. 1 survival curve by disease (Internet). 2019. http:\/\/www.jdchct.or.jp\/data\/report\/2019\/3-3-1.pdf. Accessed 29 Mar 2021."},{"issue":"9","key":"3772_CR4","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1016\/j.bbmt.2017.05.035","volume":"23","author":"A D'Souza","year":"2017","unstructured":"D\u2019Souza A, Lee S, Zhu X, Pasquini M. Current use and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant. 2017;23(9):1417\u201321.","journal-title":"Biol Blood Marrow Transplant"},{"issue":"12","key":"3772_CR5","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1016\/j.bbmt.2010.05.019","volume":"16","author":"JE Levine","year":"2010","unstructured":"Levine JE, Logan B, Wu J, Alousi AM, Ho V, Bolanos-Meade J, et al. Graft-versus-host disease treatment: predictors of survival. Biol Blood Marrow Transplant. 2010;16(12):1693\u20139.","journal-title":"Biol Blood Marrow Transplant"},{"key":"3772_CR6","unstructured":"Japanese Society for Transplantation and Cellular Therapy. Hematopoietic Cell Transplantation Guidelines\u2014GVHD (5th edn). 2022. https:\/\/www.jstct.or.jp\/uploads\/files\/guideline\/01_02_gvhd_ver05.1.pdf. Accessed 1 Aug 2023."},{"key":"3772_CR7","unstructured":"Immunosuppressant Cellcept (mycophenolate mofetil) approved for additional indication for suppression of graft-pair host-disease (GVHD) in hematopoietic stem cell transplantation. https:\/\/www.chugai-pharm.co.jp\/news\/detail\/20210625170000_1117.html. Accessed 1 Jul 2021."},{"issue":"6","key":"3772_CR8","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1016\/j.bbmt.2017.12.797","volume":"24","author":"MA Schroeder","year":"2018","unstructured":"Schroeder MA, Choi J, Staser K, DiPersio JF. The role of janus kinase signaling in graft-versus-host disease and graft versus leukemia. Biol Blood Marrow Transplant. 2018;24(6):1125\u201334.","journal-title":"Biol Blood Marrow Transplant"},{"issue":"4","key":"3772_CR9","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1080\/1744666X.2020.1740592","volume":"16","author":"H Ali","year":"2020","unstructured":"Ali H, Salhotra A, Modi B, Nakamura R. Ruxolitinib for the treatment of graft-versus-host disease. Expert Rev Clin Immunol. 2020;16(4):347\u201359. https:\/\/doi.org\/10.1080\/1744666X.2020.1740592.","journal-title":"Expert Rev Clin Immunol"},{"issue":"2","key":"3772_CR10","doi-asserted-by":"publisher","first-page":"e328","DOI":"10.1634\/theoncologist.2019-0627","volume":"25","author":"D Przepiorka","year":"2020","unstructured":"Przepiorka D, Luo L, Subramaniam S, Qiu J, Gudi R, Cunningham LC, et al. FDA approval summary: Ruxolitinib for treatment of steroid-refractory acute graft-versus-host disease. Oncologist. 2020;25(2):e328\u201334.","journal-title":"Oncologist"},{"issue":"6","key":"3772_CR11","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1093\/oncolo\/oyac042","volume":"27","author":"RQ Le","year":"2022","unstructured":"Le RQ, Wang X, Zhang H, Li H, Przepiorka D, Vallejo J, et al. FDA approval summary: Ruxolitinib for treatment of chronic graft-versus-host disease after failure of one or two lines of systemic therapy. Oncologist. 2022;27(6):493\u2013500.","journal-title":"Oncologist"},{"key":"3772_CR12","unstructured":"Novartis receives European Commission approval for Jakavi\u00ae to be the first post-steroid treatment for acute and chronic graft-versus-host disease. https:\/\/www.novartis.com\/news\/media-releases\/novartis-receives-european-commission-approval-jakavi-be-first-post-steroid-treatment-acute-and-chronic-graft-versus-host-disease. Accessed 1 Jul 2022."},{"issue":"19","key":"3772_CR13","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1056\/NEJMoa1917635","volume":"382","author":"R Zeiser","year":"2020","unstructured":"Zeiser R, von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800\u201310.","journal-title":"N Engl J Med"},{"issue":"19","key":"3772_CR14","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1056\/NEJMe2003331","volume":"382","author":"N Chao","year":"2020","unstructured":"Chao N. Finally, a successful randomized trial for GVHD. N Engl J Med. 2020;382(19):1853\u20134.","journal-title":"N Engl J Med"},{"issue":"1","key":"3772_CR15","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.bbmt.2015.09.001","volume":"22","author":"AC Harris","year":"2016","unstructured":"Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, Bunworasate U, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the mount sinai acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016;22(1):4\u201310.","journal-title":"Biol Blood Marrow Transplant"},{"issue":"5","key":"3772_CR16","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1038\/s41375-020-0804-2","volume":"34","author":"F Malard","year":"2020","unstructured":"Malard F, Huang XJ, Sim JPY. Treatment and unmet needs in steroid-refractory acute graft-versus-host disease. Leukemia. 2020;34(5):1229\u201340.","journal-title":"Leukemia"},{"issue":"4","key":"3772_CR17","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1182\/blood-2004-06-2385","volume":"105","author":"H Oh","year":"2005","unstructured":"Oh H, Loberiza FR Jr, Zhang MJ, Ringden O, Akiyama H, Asai T, et al. Comparison of graft-versus-host-disease and survival after HLA-identical sibling bone marrow transplantation in ethnic populations. Blood. 2005;105(4):1408\u201316.","journal-title":"Blood"},{"issue":"3","key":"3772_CR18","doi-asserted-by":"publisher","first-page":"125","DOI":"10.7889\/hct-16-031","volume":"6","author":"Y Najima","year":"2017","unstructured":"Najima Y, Ohashi K. Mesenchymal stem cells: the first approved stem cell drug in Japan. J Hematopoietic Cell Transpl. 2017;6(3):125\u201332.","journal-title":"J Hematopoietic Cell Transpl"},{"issue":"2","key":"3772_CR19","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1182\/bloodadvances.2018025643","volume":"3","author":"M Wakamatsu","year":"2019","unstructured":"Wakamatsu M, Terakura S, Ohashi K, Fukuda T, Ozawa Y, Kanamori H, et al. Impacts of thymoglobulin in patients with acute leukemia in remission undergoing allogeneic HSCT from different donors. Blood Adv. 2019;3(2):105\u201315.","journal-title":"Blood Adv"},{"issue":"2","key":"3772_CR20","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s12185-015-1930-x","volume":"103","author":"K Miyamura","year":"2016","unstructured":"Miyamura K. Insurance approval of mesenchymal stem cell for acute GVHD in Japan: need of follow up for some remaining concerns. Int J Hematol. 2016;103(2):155\u201364.","journal-title":"Int J Hematol"},{"issue":"22","key":"3772_CR21","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1056\/NEJMra1609337","volume":"377","author":"R Zeiser","year":"2017","unstructured":"Zeiser R, Blazar BR. Acute graft-versus-host disease\u2014biologic process, prevention, and therapy. N Engl J Med. 2017;377(22):2167\u201379.","journal-title":"N Engl J Med"},{"key":"3772_CR22","unstructured":"Mohamad Mohty C-EB, Valentin G-G, David R, Sung-Soo Y, Valerie C, Yok-Lam K, Dietger N, Reuven O, G\u00e9rard S, Nikolas von B, Robert Z, Judith X, Juliane M, Bruy\u00e8re M, Jeff S. Ruxolitinib (RUX) vs best available therapy (BAT) in patients with steroid-refractory acute GRAFT-VS HOST disease (SR-AGVHD): 6-month follow-up from the randomized, phase 3 reach2 study. In: The 47th Annual Meeting of the European Society for Blood and Marrow Transplantation; 16 Mar 2021."},{"key":"3772_CR23","unstructured":"Zeiser R, von Bubnoff N, Niederwieser D, Mohty M, Bozdag SC, Forcade E et al., (ed). Ruxolitinib versus best available therapy in patients with steroid-refractory acute graft-versus-host disease: Overall response rate by baseline characteristics in the randomized phase 3 REACH2 trial. European Hematology Association (EHA 25); 11\u201321 June 2020; Virtual. Abstract S255."},{"issue":"10","key":"3772_CR24","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.1038\/leu.2015.212","volume":"29","author":"R Zeiser","year":"2015","unstructured":"Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015;29(10):2062\u20138.","journal-title":"Leukemia"},{"issue":"20","key":"3772_CR25","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1182\/blood.2020004823","volume":"135","author":"M Jagasia","year":"2020","unstructured":"Jagasia M, Perales MA, Schroeder MA, Ali H, Shah NN, Chen YB, et al. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood. 2020;135(20):1739\u201349.","journal-title":"Blood"}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-024-03772-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-024-03772-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-024-03772-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T04:20:40Z","timestamp":1720153240000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-024-03772-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,25]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["3772"],"URL":"https:\/\/doi.org\/10.1007\/s12185-024-03772-6","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,25]]},"assertion":[{"value":"17 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 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":"TT received honoraria from Novartis, Abbvie, Astellas, NIPPON SHINYAKU, Kyowa Kirin, Bristol-Myers Squibb, Sumitomo Pharma, Merck Sharp & Dohme, Celgene, Chugai, and Janssen; research funding from Astellas, Chugai, Fuji Pharma, Kyowa Kirin, Nippon Shinyaku, Asahi Kasei Pharma, Eisai, Sumitomo Pharma, ONO, Shionogi, Priothera SA, LUCA science and Otsuka; advisory board fees from Meiji Seika Pharma, Daiichi Sankyo, Asahi Kasei Pharma, Astellas, AstraZeneca, Takeda, Janssen, Toche Diagnostics, Sumitomo Pharma, Celgene, and Sanofi; manuscript preparation support from Novartis. YO received honoraria from Novartis, Pfizer, Janssen, AsahiKasei, Abbvie, Astellas, Amgen, Chugai, Bristol-Myers Squibb, Symbio, MSD, Meiji Seika, Sumitomo Dainippon,Daiichi Sankyo, Nippon Shinyaku, IQVIA and Kyowa Kirin; research funding from Novartis, Pfizer, Janssen, Meiji Seika, Incyte, and Takara Bio. KK received consulting fees from AbbVie, AstraZeneca, Celgene, Chugai, Daiichi Sankyo, Eisai, Janssen, Novartis, and Ono; honoraria from Bristol-Myers Squibb, Celgene, Dainippon-Sumitomo, Janssen, Kyowa-Kirin, MSD, Mundi, Ono, and Takeda; and research funding from AbbVie, Celgene, Chugai, Daiichi Sankyo, Eisai, Janssen, Kyowa Kirin, Novartis, Ono, and Takeda. KT, KM, KK, ST, KF, TI, ND, MO have nothing to disclose. JK received lecture fees from Bristol-Myers Squibb, Novartis, Janssen, Chugai, and Daiichi-Sankyo. HN received payment from Novartis and Chugai. YM received grants or contracts from Asahi Kasei, Eisai, Otsuka, Kyowa Kirin, Taiho, Takeda, Chugai, Japan blood products, Nippon Kayaku, Nippon Shinyaku, Mallinckrodt, and Regimmune; and payment or Honoria from Asahi Kasei, AstraZeneca, Astellas, Amgen, AbbVie, Viatris, Eisai, MSD, Otsuka, ONO, Gilead, Kyorin, Kyowa, Kissei, Konica, Sanofi, Celgene, Bristol-Myers Squibb, Bayer, CSL Behring, Daiichi Sankyo, Sumitomo Dainippon, Takeda, Terumo, Chugai, Nippon Shinyaku, Novartis, Pfizer, Mundipharma, Human Life CORD, Meiji Seika, Janssen and Yakult Honsha. YI received honoria from Astellas Pharma, Chugai Pharmaceutical, Janssen, Kyowa Kirin, Meiji Seika Pharma, Novartis, and Sumitomo Dainippon Pharma. AM, SF and TTajima are employees of Novartis Pharma K.K., Tokyo, Japan. MW is an employee of Novartis Pharma AG, Basel, Switzerland. RZ received consulting fees from Novartis; speaker fees from Incyte, MNK, Sanofi, VectivBio, and Novartis; and participated on Data safety monitoring or advisory board for Novartis and Incyte.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}