{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:13:24Z","timestamp":1761894804538,"version":"build-2065373602"},"reference-count":13,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The study was funded by PharmaMar S.A.","award":["APL-C-001-09"],"award-info":[{"award-number":["APL-C-001-09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The phase III ADMYRE trial evaluated plitidepsin plus dexamethasone (DXM) versus DXM alone in patients with relapsed\/refractory multiple myeloma (r\/r MM). ADMYRE met its primary endpoint, showing a 35% reduction in the risk of progression or death. Methods: Results from a pre-planned subgroup of patients aged &lt;75 years are shown here. This subgroup includes most of the patients evaluated in the ADMYRE study: 145\/171 patients (84.8%) in the plitidepsin + DXM arm and 71\/84 (84.5%) patients in the DXM alone arm. Results: Compared to the overall ADMYRE population, a higher reduction was found with plitidepsin plus DXM for the risk of progression or death in the primary endpoint: 47.7% vs. 35.0% (Hazard ratio [HR] = 0.523 vs. HR = 0.6509). Higher reduction in the risk of death was also found (28.9% vs. 20.3%; HR = 0.711 vs. HR = 0.797), with a clinically meaningful 5-month difference in median overall survival (13.0 months vs. 8.1 months; p = 0.0350). The safety profile of plitidepsin plus DXM in patients aged &lt;75 years was similar to that observed in the overall population of patients treated in the ADMYRE study. The most common adverse events (all grades) related to the study treatment in patients &lt; 75 years were fatigue (39.2% of patients), gastrointestinal (nausea, 39.2%; vomiting, 19.6%; diarrhea, 14.7%), and myalgia (14.0%). Conclusions: Larger differences in efficacy outcomes while maintaining a similar safety profile, together with a novel mechanism of action, suggest that this combination can be a valid option for patients with r\/r MM aged &lt;75 years.<\/jats:p>","DOI":"10.3390\/cancers17213482","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:50:19Z","timestamp":1761785419000},"page":"3482","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Randomized Phase III Study (ADMYRE) of Plitidepsin in Combination with Dexamethasone vs. Dexamethasone Alone in Relapsed\/Refractory Multiple Myeloma: Results for Patients Aged &lt;75 Years"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2390-1218","authenticated-orcid":false,"given":"Mar\u00eda Victoria","family":"Mateos","sequence":"first","affiliation":[{"name":"Department of Hematology, University Hospital of Salamanca\/IBSAL, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5133-1422","authenticated-orcid":false,"given":"Evangelos","family":"Terpos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Clinical R&D, PharmaMar, Colmenar Viejo, 28770 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Kahatt","sequence":"additional","affiliation":[{"name":"Clinical R&D, PharmaMar, Colmenar Viejo, 28770 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Clinical R&D, PharmaMar, Colmenar Viejo, 28770 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Extremera","sequence":"additional","affiliation":[{"name":"Clinical R&D, PharmaMar, Colmenar Viejo, 28770 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Clinical R&D, PharmaMar, Colmenar Viejo, 28770 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0150-2390","authenticated-orcid":false,"given":"Vicente","family":"Alfaro","sequence":"additional","affiliation":[{"name":"Clinical R&D, PharmaMar, Colmenar Viejo, 28770 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heinz","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Wilhelminen Cancer Research Institute, Department of Medicine, Center for Oncology, Hematology and Palliative Care, Wilhelminen Hospital, 1160 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1158\/1078-0432.CCR-10-0469","article-title":"Phase II clinical and pharmacokinetic study of plitidepsin 3-h infusion every two weeks alone or with dexamethasone in relapsed and refractory multiple myeloma","volume":"16","author":"Mateos","year":"2010","journal-title":"Clin. 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Cancers, 16.","DOI":"10.3390\/cancers16172931"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/21\/3482\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T05:36:27Z","timestamp":1761888987000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/21\/3482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":13,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["cancers17213482"],"URL":"https:\/\/doi.org\/10.3390\/cancers17213482","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2025,10,29]]}}}