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(TDCA), Cambridge, MA, USA"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Cancer J."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    TOURMALINE-MM3 (NCT02181413) and -MM4 (NCT02312258) were phase 3 studies of fixed-duration, single-agent ixazomib maintenance in post-transplant (TOURMALINE-MM3)\/transplant-ineligible (TOURMALINE-MM4) patients with newly diagnosed multiple myeloma (NDMM) that demonstrated improved median progression-free survival (PFS) for ixazomib vs placebo. We present the final overall survival (OS) analyses for each study separately. In both studies, eligible patients were randomized 3:2 to receive ixazomib maintenance (3\u2009mg [cycles 1\u20134], 4\u2009mg [from cycle 5 if tolerated]) or matching placebo for \u226426 cycles, or until progressive disease\/unacceptable toxicity. At median follow-up of approximately 8 years (TOURMALINE-MM3) and 5 years (TOURMALINE-MM4), median OS was not reached in either arm in MM3 (hazard ratio [HR], 1.025; 95% confidence interval [CI], 0.789\u20131.332;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.850), and was 64.8 (ixazomib) vs 69.5 (placebo) months in MM4 (HR, 1.090; 95% CI, 0.861\u20131.381;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.473). No new safety signals were identified in either study; incidence of new primary malignancies was low. Despite meeting their primary endpoints (PFS), neither final OS analysis of TOURMALINE-MM3\/-MM4 showed statistically significant differences between fixed-duration ixazomib maintenance and placebo in patients with NDMM. The growing number of available, highly effective salvage treatments with novel mechanisms of action make demonstrating an OS advantage in front-line myeloma studies increasingly challenging.\n                  <\/jats:p>","DOI":"10.1038\/s41408-025-01411-9","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T08:15:45Z","timestamp":1764836145000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Final OS analyses from the TOURMALINE- MM3 and -MM4 RCTs of ixazomib maintenance in newly diagnosed multiple myeloma"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-3254","authenticated-orcid":false,"given":"Meletios A.","family":"Dimopoulos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-9323","authenticated-orcid":false,"given":"Sagar","family":"Lonial","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2578-8335","authenticated-orcid":false,"given":"Wee-Joo","family":"Chng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-960X","authenticated-orcid":false,"given":"Shinsuke","family":"Iida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2390-1218","authenticated-orcid":false,"given":"Mar\u00eda-Victoria","family":"Mateos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth J.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catriona","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8776-1533","authenticated-orcid":false,"given":"Kaveri","family":"Suryanarayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Labotka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5862-1833","authenticated-orcid":false,"given":"S. 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J Clin Oncol. 2021;39:2758\u201367.","journal-title":"J Clin Oncol"}],"container-title":["Blood Cancer Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41408-025-01411-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-025-01411-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-025-01411-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T10:44:41Z","timestamp":1768473881000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41408-025-01411-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,4]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1411"],"URL":"https:\/\/doi.org\/10.1038\/s41408-025-01411-9","relation":{},"ISSN":["2044-5385"],"issn-type":[{"value":"2044-5385","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,4]]},"assertion":[{"value":"3 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"MAD reports being on an advisory council or committee for and receiving honoraria from Amgen, Sanofi, Regeneron, Menarini, Takeda, GlaxoSmithKline, Bristol Myers Squibb, Janssen, Beigene, Swixx, and AstraZeneca. SL reports being on a scientific advisory board for Takeda, Amgen, Novartis, Bristol Myers Squibb, GlaxoSmithKline, Abbvie, Genentech, Pfizer, Regeneron, and Janssen; research support for clinical trials from Novartis, Bristol Myers Squibb, Janssen, and Takeda; and being on the board of directors (with stock) for TG Therapeutics (neurology and autoimmune indications). WJC has received honoraria from Amgen, Takeda, Janssen, Bristol Myers Squibb, GlaxoSmithKline, Sanofi, Pfizer, and Abbvie; and grants or funds from Janssen, Bristol Myers Squibb, Abbvie, and GlaxoSmithKline. SI reports receiving honoraria from Takeda, Pfizer, Bristol Myers Squibb, Johnson & Johnson, Sanofi, Ono, and AstraZeneca; consulting fees from Takeda, Pfizer, Bristol Myers Squibb, Johnson & Johnson, Abbvie, Novartis, AstraZeneca, and GlaxoSmithKline; and grants or funds from Takeda, Pfizer, Bristol Myers Squibb, Johnson & Johnson, Sanofi, Ono, AstraZeneca, Chugai, Shionogi, GlaxoSmithKline, Daiichi Sankyo, Abbvie, Amgen, Otsuka, Alexion, and Novartis. MVM has been on an advisory board or committee for and received honoraria from Johnson & Johnson, Bristol Myers Squibb, Sanofi, GlaxoSmithKline, Pfizer, Abbvie, Kite, Regeneron, Oncopeptides, and Menarini. CL reports employment with Takeda. KS and RL report employment and ownership of stocks and shares with Takeda. GJM, CB, and SVR report no conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15"}}