{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:29:21Z","timestamp":1786980561447,"version":"build-2736575974"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T00:00:00Z","timestamp":1633132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T00:00:00Z","timestamp":1633132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Takeda Pharmaceutical Co. Ltd."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Clin Oncol"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>TOURMALINE-MM1 was a global study that demonstrated a significant improvement in progression-free survival with ixazomib plus lenalidomide and dexamethasone compared with placebo plus lenalidomide and dexamethasone, in patients with relapsed and\/or refractory multiple myeloma. The current study was conducted to evaluate further the efficacy and safety of ixazomib plus lenalidomide and dexamethasone in Japanese patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This phase 2, open-label, single-arm, multicenter study enrolled patients aged\u2009\u2265\u200920\u00a0years with relapsed and\/or refractory multiple myeloma at 16 sites in Japan. Patients refractory to lenalidomide or proteasome inhibitor-based therapy at any line were excluded. The primary endpoint was the rate of very good partial response or better in the response-evaluable analysis set. Secondary endpoints were progression-free survival, overall response rate, duration of response, time to progression, overall survival and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 34 patients were enrolled. The rate of very good partial response or better was 50.0% (95% confidence interval 31.9\u201368.1) and the overall response rate was 84.4% (95% confidence interval 67.2\u201394.7). Median progression-free survival was 22.0\u00a0months (95% confidence interval 17.3\u2013not evaluable) and median overall survival was not estimable. The safety profile of ixazomib plus lenalidomide and dexamethasone in this study was similar to that in the TOURMALINE-MM1 study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The efficacy and safety of ixazomib plus lenalidomide and dexamethasone in Japanese patients with relapsed and\/or refractory multiple myeloma are comparable with reported TOURMALINE-MM1 study results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinicaltrials.gov identifier<\/jats:title>\n                    <jats:p>NCT02917941; date of registration September 28, 2016.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10147-021-02030-7","type":"journal-article","created":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T11:21:29Z","timestamp":1633346489000},"page":"224-233","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A phase 2, open-label, multicenter study of ixazomib plus lenalidomide and dexamethasone in adult Japanese patients with relapsed and\/or refractory multiple myeloma"],"prefix":"10.1007","volume":"27","clinical-trial-number":[{"clinical-trial-number":"nct02917941","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-960X","authenticated-orcid":false,"given":"Shinsuke","family":"Iida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Izumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Komeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Terui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Fukunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenkichi","family":"Sugiura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,2]]},"reference":[{"issue":"11","key":"2030_CR1","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1056\/NEJMra1011442","volume":"364","author":"A Palumbo","year":"2011","unstructured":"Palumbo A, Anderson K (2011) Multiple myeloma. N Engl J Med 364(11):1046\u20131060","journal-title":"N Engl J Med"},{"key":"2030_CR2","unstructured":"Japan National Cancer Center (2019). Projected cancer statistics, 2020. http:\/\/ganjoho.jp\/reg_stat\/statistics\/stat\/short_pred.html. Accessed 02 June 2021"},{"issue":"2","key":"2030_CR3","doi-asserted-by":"publisher","first-page":"197","DOI":"10.3324\/haematol.2017.174573","volume":"103","author":"F Gay","year":"2018","unstructured":"Gay F, Engelhardt M, Terpos E et al (2018) From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives. Haematologica 103(2):197\u2013211","journal-title":"Haematologica"},{"issue":"21","key":"2030_CR4","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1056\/NEJMoa070594","volume":"357","author":"M Dimopoulos","year":"2007","unstructured":"Dimopoulos M, Spencer A, Attal M et al (2007) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357(21):2123\u20132132","journal-title":"N Engl J Med"},{"issue":"9594","key":"2030_CR5","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1016\/S0140-6736(07)61537-2","volume":"370","author":"T Facon","year":"2007","unstructured":"Facon T, Mary JY, Hulin C et al (2007) Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99\u201306): a randomised trial. Lancet 370(9594):1209\u20131218","journal-title":"Lancet"},{"issue":"9","key":"2030_CR6","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1056\/NEJMoa0801479","volume":"359","author":"JF San Miguel","year":"2008","unstructured":"San Miguel JF, Schlag R, Khuageva NK et al (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 359(9):906\u2013917","journal-title":"N Engl J Med"},{"issue":"21","key":"2030_CR7","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1056\/NEJMoa070596","volume":"357","author":"DM Weber","year":"2007","unstructured":"Weber DM, Chen C, Niesvizky R et al (2007) Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 357(21):2133\u20132142","journal-title":"N Engl J Med"},{"issue":"5","key":"2030_CR8","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1007\/s12185-019-02636-8","volume":"109","author":"S Iida","year":"2019","unstructured":"Iida S, Ishida T, Murakami H et al (2019) JSH practical guidelines for hematological malignancies, 2018: III. Myeloma-1. Multiple myeloma (MM). Int J Hematol 109(5):509\u2013538","journal-title":"Int J Hematol"},{"issue":"10","key":"2030_CR9","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.6004\/jnccn.2019.0049","volume":"17","author":"SK Kumar","year":"2019","unstructured":"Kumar SK, Callander NS, Hillengass J et al (2019) NCCN guidelines insights: multiple myeloma, version 1.2020. J Natl Compr Cancer Netw 17(10):1154\u20131165","journal-title":"J Natl Compr Cancer Netw"},{"issue":"1","key":"2030_CR10","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s13045-020-00980-5","volume":"13","author":"Y Yang","year":"2020","unstructured":"Yang Y, Li Y, Gu H et al (2020) Emerging agents and regimens for multiple myeloma. J Hematol Oncol 13(1):150\u2013150","journal-title":"J Hematol Oncol"},{"issue":"20","key":"2030_CR11","doi-asserted-by":"publisher","first-page":"3043","DOI":"10.1182\/blood-2014-07-552059","volume":"124","author":"B Barlogie","year":"2014","unstructured":"Barlogie B, Mitchell A, van Rhee F et al (2014) Curing myeloma at last: defining criteria and providing the evidence. Blood 124(20):3043\u20133051","journal-title":"Blood"},{"issue":"1","key":"2030_CR12","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/nrclinonc.2014.200","volume":"12","author":"MA Dimopoulos","year":"2014","unstructured":"Dimopoulos MA, Richardson PG, Moreau P et al (2014) Current treatment landscape for relapsed and\/or refractory multiple myeloma. Nat Rev Clin Oncol 12(1):42\u201354","journal-title":"Nat Rev Clin Oncol"},{"issue":"5","key":"2030_CR13","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1158\/0008-5472.CAN-09-2766","volume":"70","author":"E Kupperman","year":"2010","unstructured":"Kupperman E, Lee EC, Cao Y et al (2010) Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Can Res 70(5):1970\u20131980","journal-title":"Can Res"},{"issue":"10168","key":"2030_CR14","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/S0140-6736(18)33003-4","volume":"393","author":"MA Dimopoulos","year":"2019","unstructured":"Dimopoulos MA, Gay F, Schjesvold F et al (2019) Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet 393(10168):253\u2013264","journal-title":"Lancet"},{"issue":"34","key":"2030_CR15","doi-asserted-by":"publisher","first-page":"4030","DOI":"10.1200\/JCO.20.02060","volume":"38","author":"MA Dimopoulos","year":"2020","unstructured":"Dimopoulos MA, \u0160pi\u010dka I, Quach H et al (2020) Ixazomib as postinduction maintenance for patients with newly diagnosed multiple myeloma not undergoing autologous stem cell transplantation: the phase III TOURMALINE-MM4 trial. J Clin Oncol 38(34):4030\u20134041","journal-title":"J Clin Oncol"},{"issue":"Supplement_1","key":"2030_CR16","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1182\/blood-2019-124409","volume":"134","author":"A Dispenzieri","year":"2019","unstructured":"Dispenzieri A, Kastritis E, Wechalekar AD et al (2019) Primary results from the phase 3 tourmaline-al1 trial of ixazomib-dexamethasone versus physician\u2019s choice of therapy in patients (Pts) with relapsed\/refractory primary systemic al amyloidosis (RRAL). Blood 134(Supplement_1):139\u2013139","journal-title":"Blood"},{"issue":"17","key":"2030_CR17","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1056\/NEJMoa1516282","volume":"374","author":"P Moreau","year":"2016","unstructured":"Moreau P, Masszi T, Grzasko N et al (2016) Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 374(17):1621\u20131634","journal-title":"N Engl J Med"},{"issue":"15","key":"2030_CR18","doi-asserted-by":"publisher","first-page":"2612","DOI":"10.1200\/JCO.2009.25.4250","volume":"28","author":"AA Chanan-Khan","year":"2010","unstructured":"Chanan-Khan AA, Giralt S (2010) Importance of achieving a complete response in multiple myeloma, and the impact of novel agents. J Clin Oncol 28(15):2612\u20132624","journal-title":"J Clin Oncol"},{"issue":"18","key":"2030_CR19","doi-asserted-by":"publisher","first-page":"4691","DOI":"10.1182\/blood-2010-10-299487","volume":"117","author":"SV Rajkumar","year":"2011","unstructured":"Rajkumar SV, Harousseau J-L, Durie B et al (2011) Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood 117(18):4691\u20134695","journal-title":"Blood"},{"key":"2030_CR20","unstructured":"U.S. Food and Drug Administration. REVLIMID Prescribing Information (2019) 4439576"},{"key":"2030_CR21","unstructured":"Revlimid capsules\u00ae (lenalidomide) (2020) Japan Package Insert.  00065995"}],"container-title":["International Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10147-021-02030-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10147-021-02030-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10147-021-02030-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T17:07:46Z","timestamp":1641402466000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10147-021-02030-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,2]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["2030"],"URL":"https:\/\/doi.org\/10.1007\/s10147-021-02030-7","relation":{},"ISSN":["1341-9625","1437-7772"],"issn-type":[{"value":"1341-9625","type":"print"},{"value":"1437-7772","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,2]]},"assertion":[{"value":"2 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Shinsuke Iida reports research funding, honoraria and fees from Takeda Pharmaceutical Company Limited, during the conduct of the study; Honoraria and fees from Ono, Celgene, Janssen, Sanofi, Daiichi Sankyo and Takeda Pharmaceutical Company Limited; research funding from AbbVie, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, GlaxoSmithKline, Ono and scholarship donations from Chugai, Kyowa Kirin, Ono, Sanofi and Takeda Pharmaceutical Company Limited, outside the submitted work. Takashi Ikeda reports honoraria and fees from Sanofi, outside the submitted work. Deborah Berg, Shinichi Fukunaga and Kenkichi Sugiura are employees of Takeda Pharmaceutical Company Limited, during the conduct of the study. Deborah Berg and Shinichi Fukunaga have stock ownership in Takeda Pharmaceutical Company Limited. Takaaki Chou has received honoraria from Takeda Pharmaceutical Company Limited, Ono, and BMS. Yasuhito Terui reports honoraria and fees from Celgene, Janssen, Merck Sharp & Dohme, Eisai, Ono, Takeda Pharmaceutical Company Limited, Chugai and AbbVie. Makoto Sasaki reports honoraria and lecture fees Takeda Pharmaceutical Company Limited. Tohru Izumi and Takuya Komeno have nothing to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All study-related documents were reviewed and approved by the local or central institutional review boards of all study sites.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Objectives and potential risks and benefits were explained to patients using the informed consent form approved by the institutional review board, with each patient having signed and dated the form before screening.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}