{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:25:53Z","timestamp":1792218353939,"version":"4.4.0"},"reference-count":30,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"22","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2021,8,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>The double-blind, placebo-controlled, phase III TOURMALINE-MM1 study demonstrated a statistically significant improvement in progression-free survival with ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd in patients with relapsed or refractory multiple myeloma. We report the final analyses for overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>Patients were randomly assigned to ixazomib-Rd (n = 360) or placebo-Rd (n = 362), stratified by number of prior therapies (1 v 2 or 3), previous proteasome inhibitor (PI) exposure (yes v no), and International Staging System disease stage (I or II v III). OS (intent-to-treat population) was a key secondary end point.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>With a median follow-up of 85 months, median OS with ixazomib-Rd versus placebo-Rd was 53.6 versus 51.6 months (hazard ratio, 0.939; P = .495). Lower hazard ratios, indicating larger magnitude of OS benefit with ixazomib-Rd versus placebo-Rd, were seen in predefined subgroups: refractory to any (0.794) or last (0.742) treatment line; age &gt; 65-75 years (0.757); International Staging System stage III (0.779); 2\/3 prior therapies (0.845); high-risk cytogenetics (0.870); and high-risk cytogenetics and\/or 1q21 amplification (0.862). Following ixazomib-Rd versus placebo-Rd, 71.7% versus 69.9% of patients received \u2265 1 anticancer therapy, of whom 24.7% versus 33.9% received daratumumab and 71.8% versus 76.9% received PIs (next-line therapy: 47.5% v 55.8%). Rates of new primary malignancies were similar with ixazomib-Rd (10.3%) and placebo-Rd (11.9%). There were no new or additional safety concerns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Median OS values in both arms were the longest reported in phase III studies of Rd-based triplets in relapsed or refractory multiple myeloma at the time of this analysis; progression-free survival benefit with ixazomib-Rd versus placebo-Rd did not translate into a statistically significant OS benefit on intent-to-treat analysis. OS benefit was greater in subgroups with adverse prognostic factors. OS interpretation was confounded by imbalances in subsequent therapies received, especially PIs and daratumumab.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.21.00972","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T03:09:57Z","timestamp":1623380997000},"page":"2430-2442","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":97,"title":["Final Overall Survival Analysis of the TOURMALINE-MM1 Phase III Trial of Ixazomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma"],"prefix":"10.1200","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-8865","authenticated-orcid":false,"given":"Paul G.","family":"Richardson","sequence":"first","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5392-9284","authenticated-orcid":false,"given":"Shaji K.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Hematology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Masszi","sequence":"additional","affiliation":[{"name":"3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7727-4307","authenticated-orcid":false,"given":"Norbert","family":"Grzasko","sequence":"additional","affiliation":[{"name":"Department of Experimental Haematooncology, Medical University of Lublin, Lublin, Poland"},{"name":"Center of Oncology of the Lublin Region St Jana z Dukli, Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7353-7034","authenticated-orcid":false,"given":"Nizar J.","family":"Bahlis","sequence":"additional","affiliation":[{"name":"Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hansson","sequence":"additional","affiliation":[{"name":"Department of Hematology, Sk\u00e5ne University Hospital, Lund, Sweden"},{"name":"Sahlgrenska Academy, G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lud\u011bk","family":"Pour","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, University Hospital Brno, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9407-6265","authenticated-orcid":false,"given":"Irwindeep","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Cross Cancer Institute, University of Alberta, Edmonton, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ganly","sequence":"additional","affiliation":[{"name":"Department of Haematology, Christchurch Hospital, Christchurch, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartrum W.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Haematology, Palmerston North Hospital, Palmerston North, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon R.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Haematology, Middlemore Hospital, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Stoppa","sequence":"additional","affiliation":[{"name":"Department of Hematology, Institut Paoli-Calmettes, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gimsing","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Garderet","sequence":"additional","affiliation":[{"name":"H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0275-2575","authenticated-orcid":false,"given":"Cyrille","family":"Touzeau","sequence":"additional","affiliation":[{"name":"University Hospital H\u00f4tel Dieu, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis K.","family":"Buadi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7565-2052","authenticated-orcid":false,"given":"Jacob P.","family":"Laubach","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cavo","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Darif","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Labotka","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Berg","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Moreau","sequence":"additional","affiliation":[{"name":"University Hospital H\u00f4tel Dieu, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2019.0049"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30756-7"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0625"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-017-9707-8"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-016-2901-x"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23933"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2017.12.012"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-013-1841-y"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.075051"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-018-0141-0"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00432-4"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0702-1"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516282"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-791228"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-299487"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.2307\/2336502"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2000.00779.x"},{"key":"b19","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-200009000-00011"},{"key":"b20","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14733"},{"key":"b21","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0711-6"},{"key":"b22","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.147"},{"key":"b23","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31680"},{"key":"b24","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.5032"},{"key":"b25","doi-asserted-by":"publisher","DOI":"10.1200\/JOP.19.00244"},{"key":"b27","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.624661"},{"key":"b28","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-017-0501-4"},{"key":"b29","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02515"},{"key":"b30","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00135-5"},{"key":"b31","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002827"},{"key":"b32","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-07732-1"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.21.00972","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T06:02:26Z","timestamp":1653804146000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.21.00972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,1]]},"references-count":30,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2021,8,1]]}},"alternative-id":["10.1200\/JCO.21.00972"],"URL":"https:\/\/doi.org\/10.1200\/jco.21.00972","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,1]]},"assertion":[{"value":"2021-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-29","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}