{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:56:46Z","timestamp":1782863806185,"version":"3.54.5"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004331","name":"Johnson and Johnson","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004331","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":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The phase 3 CEPHEUS trial was conducted in 13 countries starting December 11, 2018 in patients with newly diagnosed multiple myeloma (NDMM) who were transplant-ineligible or for whom transplantation was not planned as initial therapy. Bortezomib, lenalidomide, and dexamethasone (VRd) with daratumumab (D-VRd) provided deeper, more durable responses and lowered the risk of disease progression or death compared with VRd. This analysis evaluated the efficacy and safety of D-VRd specifically in the Japanese subpopulation of the CEPHEUS trial (D-VRd: n\u2009=\u20099; VRd: n\u2009=\u200913). At a median follow-up of 59.0\u00a0months, the overall minimal residual disease (MRD) negativity rate was 77.8% with D-VRd and 46.2% with VRd (odds ratio: 4.08 [95% confidence interval: 0.60, 27.65]). The complete response or better rate was 88.9% with D-VRd and 76.9% with VRd. Median progression-free survival was not reached in either group, with a hazard ratio of 0.34 favoring D-VRd. The sustained (\u2265\u200912\u00a0months) MRD negativity rate was 55.6% with D-VRd and 38.5% with VRd. Efficacy and safety results were similar to those observed in the global CEPHEUS population, supporting the use of D-VRd in Japanese patients with NDMM.<\/jats:p>","DOI":"10.1007\/s12185-026-04185-3","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:48:49Z","timestamp":1774615729000},"page":"104-113","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Daratumumab plus VRd in Japanese transplant-ineligible\/deferred NDMM patients: Japanese subgroup of the CEPHEUS trial"],"prefix":"10.1007","volume":"124","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7132-5337","authenticated-orcid":false,"given":"Kenshi","family":"Suzuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morio","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Takamatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kosugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadakazu","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Fujisaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Facon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Zweegman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miku","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chika","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Nakatogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Carson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad Z.","family":"Usmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"4185_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229\u201363.","journal-title":"CA Cancer J Clin"},{"key":"4185_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-83630-x","volume":"15","author":"Q Hou","year":"2025","unstructured":"Hou Q, Li X, Ma H, Fu D, Liao A. A systematic epidemiological trends analysis study in global burden of multiple myeloma and 29 years forecast. Sci Rep. 2025;15:2204.","journal-title":"Sci Rep"},{"key":"4185_CR3","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.4049\/jimmunol.1003032","volume":"186","author":"M de Weers","year":"2011","unstructured":"de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DC, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186:1840\u20138.","journal-title":"J Immunol"},{"key":"4185_CR4","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1080\/19420862.2015.1007813","volume":"7","author":"MB Overdijk","year":"2015","unstructured":"Overdijk MB, Verploegen S, B\u00f6gels M, van Egmond M, Lammerts van Bueren JJ, Mutis T, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015;7:311\u201321.","journal-title":"MAbs"},{"key":"4185_CR5","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1182\/blood-2015-12-687749","volume":"128","author":"J Krejcik","year":"2016","unstructured":"Krejcik J, Casneuf T, Nijhof IS, Verbist B, Bald J, Plesner T, et al. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016;128:384\u201394.","journal-title":"Blood"},{"key":"4185_CR6","doi-asserted-by":"publisher","first-page":"807","DOI":"10.4049\/jimmunol.1501351","volume":"197","author":"MB Overdijk","year":"2016","unstructured":"Overdijk MB, Jansen JH, Nederend M, Lammerts van Bueren JJ, Groen RW, Parren PW, et al. The therapeutic CD38 monoclonal antibody daratumumab induces programmed cell death via Fc\u03b3 receptor-mediated cross-linking. J Immunol. 2016;197:807\u201313.","journal-title":"J Immunol"},{"key":"4185_CR7","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1002\/cyto.a.23693","volume":"95","author":"HC Adams 3rd","year":"2019","unstructured":"Adams HC 3rd, Stevenaert F, Krejcik J, Van der Borght K, Smets T, Bald J, et al. High-parameter mass cytometry evaluation of relapsed\/refractory multiple myeloma patients treated with daratumumab demonstrates immune modulation as a novel mechanism of action. Cytometry A. 2019;95:279\u201389.","journal-title":"Cytometry A"},{"key":"4185_CR8","doi-asserted-by":"publisher","first-page":"2104","DOI":"10.1056\/NEJMoa1817249","volume":"380","author":"T Facon","year":"2019","unstructured":"Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380:2104\u201315.","journal-title":"N Engl J Med"},{"key":"4185_CR9","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1016\/S1470-2045(21)00466-6","volume":"22","author":"T Facon","year":"2021","unstructured":"Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22:1582\u201396.","journal-title":"Lancet Oncol"},{"key":"4185_CR10","doi-asserted-by":"crossref","unstructured":"Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, et al., ALCYONE Trial Investigators. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018; 378:518-28.","DOI":"10.1056\/NEJMoa1714678"},{"key":"4185_CR11","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/S0140-6736(19)32956-3","volume":"395","author":"MV Mateos","year":"2020","unstructured":"Mateos MV, Cavo M, Blade J, Dimopoulos MA, Suzuki K, Jakubowiak A, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet. 2020;395:132\u201341.","journal-title":"Lancet"},{"key":"4185_CR12","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0140-6736(19)31240-1","volume":"394","author":"P Moreau","year":"2019","unstructured":"Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394:29\u201338.","journal-title":"Lancet"},{"key":"4185_CR13","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1016\/S1470-2045(21)00428-9","volume":"22","author":"P Moreau","year":"2021","unstructured":"Moreau P, Hulin C, Perrot A, Arnulf B, Belhadj K, Benboubker L, et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22:1378\u201390.","journal-title":"Lancet Oncol"},{"key":"4185_CR14","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1016\/S1470-2045(24)00282-1","volume":"25","author":"P Moreau","year":"2024","unstructured":"Moreau P, Hulin C, Perrot A, Arnulf B, Belhadj K, Benboubker L, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial. Lancet Oncol. 2024;25:1003\u201314.","journal-title":"Lancet Oncol"},{"key":"4185_CR15","unstructured":"National Comprehensive Cancer Network. Multiple Myeloma (Version 2.2025). https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/myeloma.pdf. Accessed 7 May 2025."},{"key":"4185_CR16","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1056\/NEJMoa2312054","volume":"390","author":"P Sonneveld","year":"2024","unstructured":"Sonneveld P, Dimopoulos MA, Boccadoro M, Quach H, Ho PJ, Beksac M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2024;390:301\u201313.","journal-title":"N Engl J Med"},{"key":"4185_CR17","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1038\/s41591-024-03485-7","volume":"31","author":"SZ Usmani","year":"2025","unstructured":"Usmani SZ, Facon T, Hungria V, Bahlis NJ, Venner CP, Braunstein M, et al. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial. Nat Med. 2025;31:1195\u2013202.","journal-title":"Nat Med"},{"key":"4185_CR18","doi-asserted-by":"publisher","first-page":"e538","DOI":"10.1016\/S1470-2045(14)70442-5","volume":"15","author":"SV Rajkumar","year":"2014","unstructured":"Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538\u201348.","journal-title":"Lancet Oncol"},{"key":"4185_CR19","doi-asserted-by":"publisher","first-page":"2068","DOI":"10.1182\/blood-2014-12-615187","volume":"125","author":"A Palumbo","year":"2015","unstructured":"Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015;125:2068\u201374.","journal-title":"Blood"},{"key":"4185_CR20","unstructured":"International Myeloma Working Group for the prognosis of elderly myeloma patients. Myeloma Frailty Score Calculator. http:\/\/www.myelomafrailtyscorecalculator.net\/. Accessed 7 May 2025."},{"key":"4185_CR21","unstructured":"Japanese Society for Hematology. JSH practical guidelines for hematological malignancies, 2024: version 3.1. iii. Myeloma; 1. Multiple myeloma (mm). 2024. http:\/\/www.jshem.or.jp\/gui-hemali\/3_1_1.html. Accessed 7 May 2025."}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-026-04185-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-026-04185-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-026-04185-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:08:42Z","timestamp":1782860922000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-026-04185-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,27]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["4185"],"URL":"https:\/\/doi.org\/10.1007\/s12185-026-04185-3","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,27]]},"assertion":[{"value":"18 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2026","order":6,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":7,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This article has been updated to amend the corrections in tables 1, 2 and 4 layout (missing indents and changing italics).","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Kenshi Suzuki received consulting fees from SRL and lecture fees from Takeda, Ono Pharmaceutical, Novartis, Sanofi, Bristol Myers Squibb, and Janssen. Morio Matsumoto received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen Pharmaceutical, Takeda Pharmaceutical, and Sanofi K.K. Hiroyuki Takamatsu received honoraria from Janssen, Ono, Sanofi, and Bristol-Myers Squibb and consultancy fees from Adaptive Biotechnologies. Hiroshi Kosugi received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Novartis Pharma K.K., Asahi Kasei Pharma, Bristol-Myers Squibb K.K., Novo Nordisk Pharma Japan, Sanofi K.K., Kissei Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., Nippon Shinyaku Co., Ltd., Kyowa Kirin Co., Ltd., Astellas Inc., Janssen Pharmaceutical K.K., Japan Blood Products Organization, Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Beckton Dickinson K.K., and Abbvie GK. Sonja Zweegma received research support from Janssen and Takeda, and the institution they belong to received payment for participating on boards of Janssen, Sanofi, BMS, Oncopeptides, Amagen, and Abbvie. Miku Ito, Chika Sakai, and Robin Carson own stock in and are employees of Johnson & Johnson. Satoshi Kanai owns stock in Johnson & Johnson and is an employee of Johnson & Johnson Innovative Medicine. Tomohiko Nakatogawa is an employee of Johnson & Johnson. Melissa Rowe receives support for attending meetings and\/or travel, owns stock in, and is an employee of Johnson & Johnson. Saad Z. Usmani received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Amgen, BMS\/Celgene, Galapagos, Genentech, GSK, Janssen, Pfizer, Regeneron, Sanofi, and Takeda, and received research funds paid for medical research (e.g., collaborative research, funded research, clinical trial) from Abbvie, Amgen, BMS\/Celgene, GSK, Gilead, Gracell Therapeutics, Janssen, and K36 Therapeutics. Tadakazu Kondo, Tomoaki Fujisaki, and Thierry Facon have no conflicts of interest to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}