{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:51:10Z","timestamp":1790823070904,"version":"4.1.0"},"reference-count":44,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2012,8,20]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>\n                      In all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD) followed by high-dose melphalan and autologous stem-cell transplantation. Maintenance consisted of thalidomide 50 mg (VAD) once per day or bortezomib 1.3 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (PAD) once every 2 weeks for 2 years. The primary analysis was progression-free survival (PFS) adjusted for International Staging System (ISS) stage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Complete response (CR), including near CR, was superior after PAD induction (15% v 31%; P &lt; .001) and bortezomib maintenance (34% v 49%; P &lt; .001). After a median follow-up of 41 months, PFS was superior in the PAD arm (median of 28 months v 35 months; hazard ratio [HR], 0.75; 95% CI, 0.62 to 0.90; P = .002). In multivariate analysis, overall survival (OS) was better in the PAD arm (HR, 0.77; 95% CI, 0.60 to 1.00; P = .049). In high-risk patients presenting with increased creatinine more than 2 mg\/dL, bortezomib significantly improved PFS from a median of 13 months to 30 months (HR, 0.45; 95% CI, 0.26 to 0.78; P = .004) and OS from a median of 21 months to 54 months (HR, 0.33; 95% CI, 0.16 to 0.65; P &lt; .001). A benefit was also observed in patients with deletion 17p13 (median PFS, 12 v 22 months; HR, 0.47; 95% CI, 0.26 to 0.86; P = .01; median OS, 24 months v not reached at 54 months; HR, 0.36; 95% CI, 0.18 to 0.74; P = .003).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.2011.39.6820","type":"journal-article","created":{"date-parts":[[2012,7,17]],"date-time":"2012-07-17T09:20:54Z","timestamp":1342516854000},"page":"2946-2955","source":"Crossref","is-referenced-by-count":713,"title":["Bortezomib Induction and Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma: Results of the Randomized Phase III HOVON-65\/ GMMG-HD4 Trial"],"prefix":"10.1200","volume":"30","author":[{"given":"Pieter","family":"Sonneveld","sequence":"first","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo G.H.","family":"Schmidt-Wolf","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronno","family":"van der Holt","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"el Jarari","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Bertsch","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Salwender","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Zweegman","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edo","family":"Vellenga","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemiek","family":"Broyl","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor W.","family":"Blau","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja C.","family":"Weisel","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulamiet","family":"Wittebol","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard M.J.","family":"Bos","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Stevens-Kroef","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Scheid","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pfreundschuh","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Hose","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Jauch","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helgi","family":"van der Velde","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinier","family":"Raymakers","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn R.","family":"Schaafsma","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jose","family":"Kersten","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinus","family":"van Marwijk-Kooy","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Duehrsen","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Lindemann","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre W.","family":"Wijermans","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk M.","family":"Lokhorst","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut M.","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2009.0063"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199607113350204"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022340"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1011442"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1999.01279.x"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830330203"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043445"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030288"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa070594"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa070596"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0801479"},{"key":"B12","first-page":"1498","volume":"91","author":"Harousseau JL","year":"2006","journal-title":"Haematologica"},{"key":"B13","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1016\/S0140-6736(10)61424-9","volume":"376","author":"Cavo M","year":"2010","journal-title":"Lancet"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-201053"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11534"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-300970"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.28.3945"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.174"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.7561"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-222539"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-357038"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-022962"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1114138"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1114083"},{"key":"B25","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.3324\/haematol.2011.045583","volume":"96","author":"Melqvist U","year":"2011","journal-title":"Haematologica"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06639.x"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05519.x"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.2307\/2529944"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.016436"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1998.00930.x"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404284"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-379164"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032290"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.10.2509"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.9158"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-11-255620"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-009-0726-6"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-268862"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-264333"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-02-141598"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70081-X"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11463"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.28.1238"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.30.8791"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2011.39.6820","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T18:26:55Z","timestamp":1653503215000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2011.39.6820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,20]]},"references-count":44,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2012,8,20]]}},"alternative-id":["10.1200\/JCO.2011.39.6820"],"URL":"https:\/\/doi.org\/10.1200\/jco.2011.39.6820","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,20]]}}}