Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial
The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical...
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| Veröffentlicht in: | Leukemia 2018-02, Vol.32 (2), p.383-390 |
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| creator | Goldschmidt, H Lokhorst, H M Mai, E K van der Holt, B Blau, I W Zweegman, S Weisel, K C Vellenga, E Pfreundschuh, M Kersten, M J Scheid, C Croockewit, S Raymakers, R Hose, D Potamianou, A Jauch, A Hillengass, J Stevens-Kroef, M Raab, M S Broijl, A Lindemann, H W Bos, G M J Brossart, P van Marwijk Kooy, M Ypma, P Duehrsen, U Schaafsma, R M Bertsch, U Hielscher, T Jarari, Le Salwender, H J Sonneveld, P |
| description | The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18–65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65–0.89,
P
=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74–1.08,
P
=0.24). The incidence of SPM were similar between the two arms (7% each,
P
=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl
−1
) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02,
P
=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM. |
| doi_str_mv | 10.1038/leu.2017.211 |
| format | Article |
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P
=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74–1.08,
P
=0.24). The incidence of SPM were similar between the two arms (7% each,
P
=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl
−1
) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02,
P
=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2017.211</identifier><identifier>PMID: 28761118</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45 ; 692/308/2056 ; 692/308/2779/777 ; 692/699/1541/1990/804 ; Aberration ; Autografts ; Bortezomib ; Cancer Research ; Clonal deletion ; Confidence intervals ; Creatinine ; Critical Care Medicine ; Cytotoxic agents ; Cytotoxicity ; Development and progression ; Dose-response relationship ; Drug therapy ; Gene deletion ; Health risk assessment ; Hematology ; Inhibitor drugs ; Intensive ; Internal Medicine ; Kidneys ; Medicine ; Medicine & Public Health ; Melphalan ; Multiple myeloma ; Oncology ; original-article ; Patient outcomes ; Renal function ; Stem cell transplantation ; Survival ; Targeted cancer therapy ; Thalidomide ; Transplantation</subject><ispartof>Leukemia, 2018-02, Vol.32 (2), p.383-390</ispartof><rights>Macmillan Publishers Limited, part of Springer Nature. 2018</rights><rights>COPYRIGHT 2018 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Feb 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4621-f8077c53dbc469f85b4dd40d20e957a27981b5960ba8b5d45c19371754839d123</citedby><cites>FETCH-LOGICAL-c4621-f8077c53dbc469f85b4dd40d20e957a27981b5960ba8b5d45c19371754839d123</cites><orcidid>0000-0003-1277-310X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/leu.2017.211$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2017.211$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28761118$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goldschmidt, H</creatorcontrib><creatorcontrib>Lokhorst, H M</creatorcontrib><creatorcontrib>Mai, E K</creatorcontrib><creatorcontrib>van der Holt, B</creatorcontrib><creatorcontrib>Blau, I W</creatorcontrib><creatorcontrib>Zweegman, S</creatorcontrib><creatorcontrib>Weisel, K C</creatorcontrib><creatorcontrib>Vellenga, E</creatorcontrib><creatorcontrib>Pfreundschuh, M</creatorcontrib><creatorcontrib>Kersten, M J</creatorcontrib><creatorcontrib>Scheid, C</creatorcontrib><creatorcontrib>Croockewit, S</creatorcontrib><creatorcontrib>Raymakers, R</creatorcontrib><creatorcontrib>Hose, D</creatorcontrib><creatorcontrib>Potamianou, A</creatorcontrib><creatorcontrib>Jauch, A</creatorcontrib><creatorcontrib>Hillengass, J</creatorcontrib><creatorcontrib>Stevens-Kroef, M</creatorcontrib><creatorcontrib>Raab, M S</creatorcontrib><creatorcontrib>Broijl, A</creatorcontrib><creatorcontrib>Lindemann, H W</creatorcontrib><creatorcontrib>Bos, G M J</creatorcontrib><creatorcontrib>Brossart, P</creatorcontrib><creatorcontrib>van Marwijk Kooy, M</creatorcontrib><creatorcontrib>Ypma, P</creatorcontrib><creatorcontrib>Duehrsen, U</creatorcontrib><creatorcontrib>Schaafsma, R M</creatorcontrib><creatorcontrib>Bertsch, U</creatorcontrib><creatorcontrib>Hielscher, T</creatorcontrib><creatorcontrib>Jarari, Le</creatorcontrib><creatorcontrib>Salwender, H J</creatorcontrib><creatorcontrib>Sonneveld, P</creatorcontrib><title>Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18–65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65–0.89,
P
=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74–1.08,
P
=0.24). The incidence of SPM were similar between the two arms (7% each,
P
=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl
−1
) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02,
P
=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.</description><subject>45</subject><subject>692/308/2056</subject><subject>692/308/2779/777</subject><subject>692/699/1541/1990/804</subject><subject>Aberration</subject><subject>Autografts</subject><subject>Bortezomib</subject><subject>Cancer Research</subject><subject>Clonal deletion</subject><subject>Confidence intervals</subject><subject>Creatinine</subject><subject>Critical Care Medicine</subject><subject>Cytotoxic agents</subject><subject>Cytotoxicity</subject><subject>Development and progression</subject><subject>Dose-response relationship</subject><subject>Drug therapy</subject><subject>Gene deletion</subject><subject>Health risk assessment</subject><subject>Hematology</subject><subject>Inhibitor drugs</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Kidneys</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Melphalan</subject><subject>Multiple myeloma</subject><subject>Oncology</subject><subject>original-article</subject><subject>Patient outcomes</subject><subject>Renal function</subject><subject>Stem cell transplantation</subject><subject>Survival</subject><subject>Targeted cancer therapy</subject><subject>Thalidomide</subject><subject>Transplantation</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNpt0kFv0zAUB3ALgVg3uHFGlpAQB9zZThzb3MaAttJGL8DVcpKXJpMTFztB6j49jjpgQ5MPlu3fe_KT_gi9YnTJaKbOHUxLTplccsaeoAXLZUGEEOwpWlClJCk0z0_QaYw3lM6PxXN0wpUsGGNqgX599GGEW993JS6h8QGwHWpsmxECbrtdS2ofAY8tBLs_4G7A_QGc7-0H7PywI4n1OECc3BhxE3w_U7xvbSrabDZ4vf2x_UoKcb66vl6R9accj6Gz7gV61lgX4eXdfoa-f_n87XJNrrarzeXFFanygjPSKCplJbK6TGfdKFHmdZ3TmlPQQloutWKl0AUtrSpFnYuK6UwyKXKV6Zrx7Ay9O_bdB_9zgjiavosVOGcH8FM0THPBZcYzkeib_-iNn8KQfpeUFlxoqtg_tbMOTDc0fgy2mpuaC8ELkQnFi6SWj6i0aui7yg_QdOn-QcHbewUtWDe20btp7PwQH8L3R1gFH2OAxuxD19twMIyaOQ8m5cHMeTApD4m_vhtqKnuo_-I_AUiAHEFMT8MOwr2pH2v4GytDudo</recordid><startdate>20180201</startdate><enddate>20180201</enddate><creator>Goldschmidt, H</creator><creator>Lokhorst, H M</creator><creator>Mai, E 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before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial</title><author>Goldschmidt, H ; Lokhorst, H M ; Mai, E K ; van der Holt, B ; Blau, I W ; Zweegman, S ; Weisel, K C ; Vellenga, E ; Pfreundschuh, M ; Kersten, M J ; Scheid, C ; Croockewit, S ; Raymakers, R ; Hose, D ; Potamianou, A ; Jauch, A ; Hillengass, J ; Stevens-Kroef, M ; Raab, M S ; Broijl, A ; Lindemann, H W ; Bos, G M J ; Brossart, P ; van Marwijk Kooy, M ; Ypma, P ; Duehrsen, U ; Schaafsma, R M ; Bertsch, U ; Hielscher, T ; Jarari, Le ; Salwender, H J ; Sonneveld, 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Medicine</topic><topic>Kidneys</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Melphalan</topic><topic>Multiple myeloma</topic><topic>Oncology</topic><topic>original-article</topic><topic>Patient outcomes</topic><topic>Renal function</topic><topic>Stem cell transplantation</topic><topic>Survival</topic><topic>Targeted cancer therapy</topic><topic>Thalidomide</topic><topic>Transplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goldschmidt, H</creatorcontrib><creatorcontrib>Lokhorst, H M</creatorcontrib><creatorcontrib>Mai, E K</creatorcontrib><creatorcontrib>van der Holt, B</creatorcontrib><creatorcontrib>Blau, I W</creatorcontrib><creatorcontrib>Zweegman, S</creatorcontrib><creatorcontrib>Weisel, K C</creatorcontrib><creatorcontrib>Vellenga, E</creatorcontrib><creatorcontrib>Pfreundschuh, M</creatorcontrib><creatorcontrib>Kersten, M J</creatorcontrib><creatorcontrib>Scheid, 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goldschmidt, H</au><au>Lokhorst, H M</au><au>Mai, E K</au><au>van der Holt, B</au><au>Blau, I W</au><au>Zweegman, S</au><au>Weisel, K C</au><au>Vellenga, E</au><au>Pfreundschuh, M</au><au>Kersten, M J</au><au>Scheid, C</au><au>Croockewit, S</au><au>Raymakers, R</au><au>Hose, D</au><au>Potamianou, A</au><au>Jauch, A</au><au>Hillengass, J</au><au>Stevens-Kroef, M</au><au>Raab, M S</au><au>Broijl, A</au><au>Lindemann, H W</au><au>Bos, G M J</au><au>Brossart, P</au><au>van Marwijk Kooy, M</au><au>Ypma, P</au><au>Duehrsen, U</au><au>Schaafsma, R M</au><au>Bertsch, U</au><au>Hielscher, T</au><au>Jarari, Le</au><au>Salwender, H J</au><au>Sonneveld, P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2018-02-01</date><risdate>2018</risdate><volume>32</volume><issue>2</issue><spage>383</spage><epage>390</epage><pages>383-390</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18–65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65–0.89,
P
=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74–1.08,
P
=0.24). The incidence of SPM were similar between the two arms (7% each,
P
=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl
−1
) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02,
P
=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28761118</pmid><doi>10.1038/leu.2017.211</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-1277-310X</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2018-02, Vol.32 (2), p.383-390 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1925273235 |
| source | SpringerLink Journals; Nature Journals Online |
| subjects | 45 692/308/2056 692/308/2779/777 692/699/1541/1990/804 Aberration Autografts Bortezomib Cancer Research Clonal deletion Confidence intervals Creatinine Critical Care Medicine Cytotoxic agents Cytotoxicity Development and progression Dose-response relationship Drug therapy Gene deletion Health risk assessment Hematology Inhibitor drugs Intensive Internal Medicine Kidneys Medicine Medicine & Public Health Melphalan Multiple myeloma Oncology original-article Patient outcomes Renal function Stem cell transplantation Survival Targeted cancer therapy Thalidomide Transplantation |
| title | Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T04%3A34%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Bortezomib%20before%20and%20after%20high-dose%20therapy%20in%20myeloma:%20long-term%20results%20from%20the%20phase%20III%20HOVON-65/GMMG-HD4%20trial&rft.jtitle=Leukemia&rft.au=Goldschmidt,%20H&rft.date=2018-02-01&rft.volume=32&rft.issue=2&rft.spage=383&rft.epage=390&rft.pages=383-390&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/leu.2017.211&rft_dat=%3Cgale_proqu%3EA526535826%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1995259081&rft_id=info:pmid/28761118&rft_galeid=A526535826&rfr_iscdi=true |