Matches in SemOpenAlex for { <https://semopenalex.org/work/W2984667065> ?p ?o ?g. }
- W2984667065 endingPage "3308" @default.
- W2984667065 startingPage "3308" @default.
- W2984667065 abstract "Background: Novel agents such as IMIDs and proteasome inhibitors have substantially changed the therapeutic landscape in the first line treatment of multiple myeloma (MM). Better response rates and prolonged progression-free survival have lead to an improvement in overall survival (OS) with median values well beyond 5 years. Therefore to assess whether first line therapy strategies have an impact on the prognosis for patients with MM, long-term results of clinical trials with follow up covering >10 years are necessary. Methods: The HOVON-65/GMMG-HD4 study is a prospective randomized trial testing bortezomib+adriamycin+dexamethasone (PAD) for 3 cycles as induction prior to high-dose chemotherapy (HDT) and autologous stem cell transplantation compared to vincristine+adriamycin+dexamethasone (VAD) in the control arm. After one (HOVON) or two (GMMG) HDT maintenance was given for 2 years consisting of bortezomib every 2 weeks in the PAD arm and thalidomide 50 mg daily in the VAD arm. The study results were initially reported in 2012 (1) and with a median follow up of 91 months in 2018 (2). In this analysis we present OS results after a median follow up of 137 months. All hazard ratios (HR) are given with 95% confidence intervals (CI). Results: Overall survival at 12 years was 32% (CI 27-37%) in the VAD arm versus 36% (CI 31-41%) in the PAD arm without significant difference in the univariate Cox model (HR 0.87, CI 0.73 - 1.03, p=0. 11 or in multivariate Cox model including ISS stage and treatment arm (HR 0.87, CI 0.73 - 1.04, p=0.12; the primary analysis) as specified in the study protocol. When other factors including age, sex, ISS stage, WHO performance status, Immunoglobulin-type, Durie and Salmon-stage, LDH, del 13q, study group and renal impairment (RI, defined as serum creatinine ≥ 2 mg/dl) were added to the Cox model, treatment in the PAD arm was a significant factor for improved OS (HR 0.84, CI 0.7 - 1.0, p=0.048). Of the remaining factors age (HR 1.02, CI 1.01 - 1.03, p=0.002), female sex (HR 0.83, CI 0.69 - 0.99, p=0.044), ISS stage (HR 1.19, CI 1.04 - 1.35, p=0.01), WHO performance status (HR 1.32, CI 1.17 - 1.48, p<0.001), IgA (HR 1.56, CI 1.18 - 2.06, p=0.002), LDH>ULN (HR 1.44, CI 1.14 - 1.82, p=0.002), del 13q (HR 1.42, CI 1.17 - 1.73, p<0.001) and RI (HR 1.42, CI 1.04 - 1.95, p=0.026) were significantly associated with OS. Tests for heterogeneity revealed two factors as significant: RI and del17p (only fully evaluated for the GMMG cohort). For patients with RI the OS probability at 12 years was 39% in the PAD arm versus 5% in the VAD arm (HR 0.34, CI 0.20 - 0.59, p<0.0001, Fig. 1). 12 year OS in patients without RI was 36% in the PAD arm and 35% in the VAD arm without significant difference (HR 0.97, CI 0.81 - 1.17, p=0.77, Fig,1). In the GMMG cohort (receiving tandem-HDT) del17p results were available and patients with del17p had a significantly better OS in the PAD arm than in the VAD arm (HR 0.36, CI 0.17 - 0.77, p=0.006), while no significant difference between treatment arms was found in patients without del17p (HR 1.01, CI 0.75 - 1.37, p=0.92). Discussion: Long-term results of the HOVON-65/GMMG-HD4 trial show that one third of patients receiving HDT with either thalidomide-based or bortezomib-based maintenance are still alive at 12 years. In contrast to earlier analyses with shorter follow up (1,2) the use of bortezomib in the induction and maintenance treatment provided a significant OS benefit when adjusting for other risk in a multivariate Cox model, although not in the primary analysis. A particular OS benefit was found in patients with RI receiving bortezomib before and after HDT and this could completely abolish the negative prognostic impact of RI. Similarly bortezomib used in combination with tandem-HDT improved OS in patients with del17p so that more than a third of these patients with high-risk MM survived more than 10 years. Our results underline that despite the growing options for treatment at relapse the choice of an optimal first-line therapy is of critical prognostic importance, in particular for patients with high-risk myeloma. References: 1) Sonneveld et al., J Clin Oncol, 2012; 30:2946-2955 2) Goldschmidt et al., Leukemia 2018; 32: 383-390 Figure 1 Disclosures Scheid: Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Bertsch:Celgene: Other: travel support; Sanofi: Other: travel support. Zweegman:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding. Weisel:Celgene: Consultancy, Honoraria, Research Funding; Juno: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; GSK: Honoraria; Adaptive Biotech: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria. Kersten:Gilead: Honoraria; Kite Pharma: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Novartis: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Miltenyi: Honoraria; Roche: Honoraria, Research Funding; Takeda Oncology: Research Funding; Celgene: Honoraria, Research Funding. Mai:Mundipharma: Other: travel support; Takeda: Honoraria, Other: travel support, Research Funding; Janssen: Consultancy, Honoraria, Other: travel support; Celgene: Consultancy, Honoraria, Other: travel support. Hillengass:Amgen: Consultancy, Honoraria; Janssen: Honoraria. Stilgenbauer:AbbVie, AstraZeneca, Celgene, Gilead Sciences, Inc., GSK, Hoffmann La-Roche, Janssen, Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Broyl:Celgene, amgen, Janssen,Takeda: Honoraria. Bos:Kiadis Pharma: Other: Shareholder (of Cytosen, acquired by Kiadis); Celgene: Research Funding. Dührsen:Amgen: Consultancy, Honoraria, Research Funding; CPT: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Roche: Honoraria, Research Funding; Teva: Honoraria; Novartis: Consultancy, Honoraria; Alexion: Honoraria; Gilead: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Honoraria; Celgene: Research Funding. Salwender:Celgene: Honoraria, Other: Travel or accommodations; Sanofi: Honoraria, Other: Travel or accommodations; Takeda: Honoraria, Other: Travel or accommodations; Bristol-Myers Squibb: Honoraria, Other: Travel or accommodations; AbbVie: Honoraria; Amgen: Honoraria, Other: Travel or accommodations; Janssen Cilag: Honoraria, Other: Travel or accommodations. Goldschmidt:Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Molecular Partners: Research Funding; Dietmar-Hopp-Stiftung: Research Funding; Mundipharma: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; John-Hopkins University: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Honoraria, Research Funding; John-Hopkins University: Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Research Funding; Janssen: Consultancy, Research Funding. Sonneveld:Amgen: Honoraria, Research Funding; BMS: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; SkylineDx: Research Funding. OffLabel Disclosure: bortezomib maintenance thalidomide maintenance" @default.
- W2984667065 created "2019-11-22" @default.
- W2984667065 creator A5002972322 @default.
- W2984667065 creator A5007067641 @default.
- W2984667065 creator A5012101669 @default.
- W2984667065 creator A5014277422 @default.
- W2984667065 creator A5015972472 @default.
- W2984667065 creator A5019564821 @default.
- W2984667065 creator A5019866348 @default.
- W2984667065 creator A5022522496 @default.
- W2984667065 creator A5023943397 @default.
- W2984667065 creator A5032770450 @default.
- W2984667065 creator A5036293139 @default.
- W2984667065 creator A5037330439 @default.
- W2984667065 creator A5039853793 @default.
- W2984667065 creator A5050532707 @default.
- W2984667065 creator A5051124529 @default.
- W2984667065 creator A5055916434 @default.
- W2984667065 creator A5056743174 @default.
- W2984667065 creator A5058429057 @default.
- W2984667065 creator A5060295441 @default.
- W2984667065 creator A5062881120 @default.
- W2984667065 creator A5064702344 @default.
- W2984667065 creator A5067657650 @default.
- W2984667065 creator A5068472643 @default.
- W2984667065 creator A5070221339 @default.
- W2984667065 creator A5073604089 @default.
- W2984667065 creator A5080019543 @default.
- W2984667065 creator A5080712446 @default.
- W2984667065 creator A5082157943 @default.
- W2984667065 creator A5083385949 @default.
- W2984667065 creator A5087348033 @default.
- W2984667065 creator A5087955804 @default.
- W2984667065 date "2019-11-13" @default.
- W2984667065 modified "2023-10-03" @default.
- W2984667065 title "Bortezomib-Based Induction and Maintenance Overcomes the Negative Prognostic Impact of Renal Impairment and del17p in Transplant-Eligible Myeloma Patients: Long Term Results from the Phase III HOVON-65/GMMG-HD4 Study after Median 137 Months Follow up" @default.
- W2984667065 doi "https://doi.org/10.1182/blood-2019-129684" @default.
- W2984667065 hasPublicationYear "2019" @default.
- W2984667065 type Work @default.
- W2984667065 sameAs 2984667065 @default.
- W2984667065 citedByCount "3" @default.
- W2984667065 countsByYear W29846670652020 @default.
- W2984667065 countsByYear W29846670652022 @default.
- W2984667065 crossrefType "journal-article" @default.
- W2984667065 hasAuthorship W2984667065A5002972322 @default.
- W2984667065 hasAuthorship W2984667065A5007067641 @default.
- W2984667065 hasAuthorship W2984667065A5012101669 @default.
- W2984667065 hasAuthorship W2984667065A5014277422 @default.
- W2984667065 hasAuthorship W2984667065A5015972472 @default.
- W2984667065 hasAuthorship W2984667065A5019564821 @default.
- W2984667065 hasAuthorship W2984667065A5019866348 @default.
- W2984667065 hasAuthorship W2984667065A5022522496 @default.
- W2984667065 hasAuthorship W2984667065A5023943397 @default.
- W2984667065 hasAuthorship W2984667065A5032770450 @default.
- W2984667065 hasAuthorship W2984667065A5036293139 @default.
- W2984667065 hasAuthorship W2984667065A5037330439 @default.
- W2984667065 hasAuthorship W2984667065A5039853793 @default.
- W2984667065 hasAuthorship W2984667065A5050532707 @default.
- W2984667065 hasAuthorship W2984667065A5051124529 @default.
- W2984667065 hasAuthorship W2984667065A5055916434 @default.
- W2984667065 hasAuthorship W2984667065A5056743174 @default.
- W2984667065 hasAuthorship W2984667065A5058429057 @default.
- W2984667065 hasAuthorship W2984667065A5060295441 @default.
- W2984667065 hasAuthorship W2984667065A5062881120 @default.
- W2984667065 hasAuthorship W2984667065A5064702344 @default.
- W2984667065 hasAuthorship W2984667065A5067657650 @default.
- W2984667065 hasAuthorship W2984667065A5068472643 @default.
- W2984667065 hasAuthorship W2984667065A5070221339 @default.
- W2984667065 hasAuthorship W2984667065A5073604089 @default.
- W2984667065 hasAuthorship W2984667065A5080019543 @default.
- W2984667065 hasAuthorship W2984667065A5080712446 @default.
- W2984667065 hasAuthorship W2984667065A5082157943 @default.
- W2984667065 hasAuthorship W2984667065A5083385949 @default.
- W2984667065 hasAuthorship W2984667065A5087348033 @default.
- W2984667065 hasAuthorship W2984667065A5087955804 @default.
- W2984667065 hasBestOaLocation W29846670651 @default.
- W2984667065 hasConcept C126322002 @default.
- W2984667065 hasConcept C143998085 @default.
- W2984667065 hasConcept C2776364478 @default.
- W2984667065 hasConcept C2777478702 @default.
- W2984667065 hasConcept C71924100 @default.
- W2984667065 hasConceptScore W2984667065C126322002 @default.
- W2984667065 hasConceptScore W2984667065C143998085 @default.
- W2984667065 hasConceptScore W2984667065C2776364478 @default.
- W2984667065 hasConceptScore W2984667065C2777478702 @default.
- W2984667065 hasConceptScore W2984667065C71924100 @default.
- W2984667065 hasIssue "Supplement_1" @default.
- W2984667065 hasLocation W29846670651 @default.
- W2984667065 hasOpenAccess W2984667065 @default.
- W2984667065 hasPrimaryLocation W29846670651 @default.
- W2984667065 hasRelatedWork W1967132861 @default.
- W2984667065 hasRelatedWork W2063424779 @default.
- W2984667065 hasRelatedWork W2104965094 @default.
- W2984667065 hasRelatedWork W2136773918 @default.
- W2984667065 hasRelatedWork W2344741804 @default.
- W2984667065 hasRelatedWork W2377458274 @default.
- W2984667065 hasRelatedWork W2409439928 @default.
- W2984667065 hasRelatedWork W3028919400 @default.