B152 First Analysis of HOVON-65/GMMG-HD4 Randomized Phase III Trial Comparing Bortezomib, Doxorubicin, Dexamethasone (PAD) vs. VAD as Induction Treatment Prior to High-dose Melphalan (HDM) in Patients with Newly Diagnosed Multiple Myeloma (MM)

Sonneveld, Pieter; Eljarari, L; Salwender, Hans; Vellenga, Edo; Holt, Bronno van der; Schmidt-Wolf, I.; Bertsch, Uta; Schubert, J; Blau, Igor W; Gao, Jie; Beverloo, Berna; Jauch, Anna; Hose, Dirk; Schaafsma, Ron; Kersten, M.J.; Delforge, Michel; Weerdt, Okke de; Griend, René van der; Wijermans, Pierre W.; Martin, Harry; Velde, H Van der; Lokhorst, Henk M.; Goldschmidt, Hartmut

doi:10.1016/s1557-9190(11)70667-9

Cited by 56 publications

(93 citation statements)

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“…[74][75][76] With the addition of a third agent, post-ASCT CR rates may reach 15% to 40%, whereas CR/VGPR rates are 50% to 75%. [77][78][79][80] However, it is clear that compared with VGPR, the CR level is associated with a better outcome. 25,81 Currently, CR defined by the absence of M-component on immunofixation and a normal bone marrow negative is the most widely accepted level.…”

Section: Which Level Of Response Is Necessary?mentioning

confidence: 99%

The role of complete response in multiple myeloma

Harousseau

Attal

Avet-Loiseau

2009

Blood

208

148

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In multiple myeloma (MM), the impact of complete response (CR) could be shown only after introduction of high-dose therapy plus autologous stem cell transplantation (ASCT). In the context of ASCT, achieving CR (negative immunofixation and normal bone marrow) or at least very good partial response is associated with longer progression-free survival and in most studies longer survival. With novel agents, high CR rates are achieved and this prognostic impact of CR is being shown as well, both in relapsed and in newly diagnosed MM. However the benefit of CR achievement depends on the type of treatment and is not identical for all patients. In elderly patients, treatments inducing more CR may be more toxic. Although CR achievement is necessary in patients with poor-risk disease, it might not be as critical for long survival in more indolent MM. CR achievement is not the only objective of treatment because it is possible to further improve the depth of response and the outcome by continuing treatment after CR achievement. Finally, there are several levels of CR and in the future it will be necessary to confirm the prognostic impact of immunophenotypic or molecular CR or of CR defined by imaging procedures. (Blood. 2009;114: 3139-3146)

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Section: Which Level Of Response Is Necessary?mentioning

confidence: 99%

The role of complete response in multiple myeloma

Harousseau

Attal

Avet-Loiseau

2009

Blood

208

148

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“…22 This trial is a large multicenter, prospective, randomized phase III trial, evaluating bortezomib as front-line treatment (EudraCT n. 2004-000944-26; registered at www.trialregister.nl as NTR213) 20 . Gene expression profiles of the APEX, SUMMIT and CREST trials have been collectively described.…”

Section: Patientsmentioning

confidence: 99%

“…Here, the expression of 123 CTAs, spanning these categories, was further evaluated in relapse cases and in newly diagnosed MM. [20][21][22] …”

Section: Introductionmentioning

confidence: 99%

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Duin¹,

Broyl²,

Knegt³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundIn multiple myeloma, expression of cancer testis antigens may provide prognostic markers and potential targets for immunotherapy. Expression at relapse has not yet been evaluated for a large panel of cancer testis antigens which can be classified by varying expression in normal tissue: restricted to testis, expressed in testis and brain and not restricted but selectively expressed in testis. Design and MethodsEvaluation of cancer testis antigen expression was made in newly diagnosed multiple myeloma cases (HOVON-65/GMMG-HD4 trial; n=320) and in relapse cases (APEX, SUMMIT, CREST trials; n=264). Presence of expression using Affymetrix GeneChips was determined for 123 cancer testis antigens. Of these 87 had a frequency of more than 5% in the newly diagnosed and relapsed patients, and were evaluated in detail. ResultsTissue restriction was known for 58 out of 87 cancer testis antigens. A significantly lower frequency of presence calls in the relapsed compared to newly diagnosed cases was found for 3 out of 13 testis restricted genes, 2 out of 7 testis/brain restricted genes, and 17 out of 38 testis selective genes. MAGEC1, MAGEB2 and SSX1 were the most frequent testis-restricted cancer testis antigens in both data sets. Multivariate analysis demonstrated that presence of MAGEA6 and CDCA1 were clearly associated with shorter progression free survival, and presence of MAGEA9 with shorter overall survival in the set of newly diagnosed cases. In the set of relapse cases, presence of CTAG2 was associated with shorter progression free survival and presence of SSX1 with shorter overall survival. ConclusionsRelapsed multiple myeloma reveals extensive cancer testis antigen expression. Cancer testis antigens are confirmed as useful prognostic markers in newly diagnosed multiple myeloma patients and in relapsed multiple myeloma patients.The HOVON-65/GMMG-HD4 trial is registered under Dutch trial register n. respectively.

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“…Bortezomib maintenance improves response rates following ASCT (Benevolo et al, 2011;Kim et al, 2012), and is also beneficial in patients ineligible for transplantation (Mateos et al, 2010;Palumbo et al, 2010). Importantly it prolongs PFS compared to thalidomide maintenance in patients receiving PAD (bortezomib, doxrubicin, dexamethasone) vs. VAD induction prior to ASCT (Sonneveld et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Improved response with post‐ASCT consolidation by low dose thalidomide, cyclophosphamide and dexamethasone as first line treatment for multiple myeloma

et al. 2012

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SummaryThe use of consolidation or maintenance to improve disease response, and hence clinical outcome, following autologous stem cell transplantation (ASCT) remains the subject of intense clinical research. We carried out a single-arm study to assess the toxicity and efficacy of a short block of consolidation therapy with cyclophosphamide, low dose thalidomide and dexamethasone (CTD) in patients within 6 months following ASCT, as part of frontline therapy for symptomatic multiple myeloma. Forty-five patients who had not progressed were enrolled on the study, and 43 completed treatment on protocol. This regimen was well tolerated soon after ASCT, with only grade 1/2 toxicity apart from neutropenia, and no long-term sequelae. Importantly, CTD consolidation improved the depth of response in treated patients, increasing the complete/very good partial response rate from 44% at 3 months, to 72% at 12 months, which was significantly higher compared with a historical group of control patients (P = 0·002). There was a trend to longer progression-free survival that favoured the study group. Consolidation therapy did not adversely affect subsequent disease response to salvage therapies at relapse. We conclude that CTD consolidation may be a useful, non-toxic and cost-effective strategy to deepen disease response following ASCT, and deserves further study in a randomized trial.

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B152 First Analysis of HOVON-65/GMMG-HD4 Randomized Phase III Trial Comparing Bortezomib, Doxorubicin, Dexamethasone (PAD) vs. VAD as Induction Treatment Prior to High-dose Melphalan (HDM) in Patients with Newly Diagnosed Multiple Myeloma (MM)

Cited by 56 publications

References 0 publications

The role of complete response in multiple myeloma

The role of complete response in multiple myeloma

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Improved response with post‐ASCT consolidation by low dose thalidomide, cyclophosphamide and dexamethasone as first line treatment for multiple myeloma

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