Bortezomib Plus Dexamethasone Is Superior to Vincristine Plus Doxorubicin Plus Dexamethasone As Induction Treatment Prior to Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: Results of the IFM 2005-01 Phase III Trial

Harousseau, Jean‐Luc; Attal, Michel; Avet-Loiseau, Hervé; Marit, Gérald; Caillot, Denis; Mohty, Mohamad; Lenain, Pascal; Hulin, Cyrille; Façon, Thierry; Casassus, Philippe; Michallet, Mauricette; Maisonneuve, Hervé; Benboubker, Lotfi; Maloisel, Frédéric; Petillon, Marie-Odile; Webb, Iain J.; Mathiot, Claire; Moreau, Philippe

doi:10.1200/jco.2009.27.9158

Cited by 502 publications

(388 citation statements)

References 42 publications

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“…Harousseau et al compared bortezomib plus dexamethasone (VD) versus vincristine, Adriamycin, dexamethasone (VAD) as pretransplant induction therapy [56]. Post-induction very good partial response (VGPR) was superior with VD compared with VAD, 38% versus 15%, respectively.…”

Section: Risk-adapted Therapymentioning

confidence: 99%

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

2013

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Disease overviewMultiple myeloma accounts for approximately 10% of hematologic malignancies.DiagnosisThe diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of associated end‐organ damage. In addition, the presence of 60% or more clonal plasma cells in the marrow is also considered as myeloma regardless of the presence or absence of end‐organ damage.Risk stratificationIn the absence of concurrent trisomies, patients with 17p deletion, t(14;16), and t(14;20) are considered to have high‐risk myeloma. Patients with t(4;14) translocation are considered intermediate‐risk. All others are considered as standard‐risk.Risk‐adapted initial therapyStandard‐risk patients can be treated with lenalidomide plus low‐dose dexamethasone (Rd), or a bortezomib‐containing triplet such as bortezomib, cyclophosphamide, dexamethasone (VCD). Intermediate‐risk and high‐risk patients require a bortezomib‐based triplet regimen. In eligible patients, initial therapy is given for approximately 4 months followed by autologous stem cell transplantation (ASCT). Standard‐risk patients can opt for delayed ASCT if stem cells can be cryopreserved. In patients are not candidates for transplant, initial therapy is given for approximately 12–18 months.Maintenance therapyAfter initial therapy, lenalidomide maintenance is considered for standard‐risk patients who are not in very good partial response or better, while maintenance with a bortezomib‐based regimen should be considered in pateints with intermediate or high‐risk myeloma.Management of refractory diseasePatients with indolent relapse can be treated first with two‐drug or three‐drug combinations. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Am. J. Hematol. 88:225–235, 2013. © 2013 Wiley Periodicals, Inc.

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Section: Risk-adapted Therapymentioning

confidence: 99%

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

2013

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“…[1][2][3] Over the last decade, novel drugs, particularly immunomodulatory (IMID) agents and proteasome inhibitors, have been incorporated into the pre-transplantation induction therapy and have improved the rate of complete response both before and after autologous transplantation. [4][5][6] The use of the IMID lenalidomide in the induction regimen was early identified as a risk factor for poor AHSC mobilization. [7][8][9][10] This negative effect, noticed particularly with growth factor mobilization, is at least partially overcome with the use of chemotherapy mobilization, [11][12][13] although this strategy carries higher cost and toxicity.…”

Section: Introductionmentioning

confidence: 99%

Growth factor plus preemptive (‘just-in-time’) plerixafor successfully mobilizes hematopoietic stem cells in multiple myeloma patients despite prior lenalidomide exposure

Costa

Abbas

Hogan

et al. 2012

Bone Marrow Transplant

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“…The benefit conferred by thalidomide combinations in induction was confirmed by the Myeloma IX and Total Therapy 2 trials (Morgan et al, 2012;Barlogie et al, 2006b). The IFM 2005-01 trial demonstrated that bortezomib and dexamethasone was also superior to VAD, increasing the pre-ASCT response rate to 79% from 63%, (Harousseau et al, 2010), and a similar improvement with bortezomib-based induction was observed in the HOVON65/GMMGHD4 trial (Sonneveld et al, 2012). Cavo et al tested the addition of bortezomib to thalidomide plus dexamethasone, and this combination of both IMiD and proteasome inhibitor significantly improved both pre-ASCT ORR (93% vs. 79%) and progression-free survival (PFS) (Cavo et al, 2010).…”

Section: Novel Agent Inductionmentioning

confidence: 75%

Augmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma

Maybury

Cook

Pratt

et al. 2016

Biology of Blood and Marrow Transplantation

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SummaryConsolidation with high dose chemotherapy and autologous stem cell transplantation (ASCT) is the standard of care for transplant eligible patients with multiple myeloma, based on randomised trials showing improved progression free survival with autologous transplantation following combination chemotherapy induction. These trials were performed before novel agents were introduced, and subsequently combinations of immunomodulatory drugs (IMiDs) and proteasome inhibitors as induction therapy have significantly improved rates and depth of response. Ongoing randomised trials are testing whether conventional autologous transplantation continues to improve responses following novel agent induction. While these results are awaited, it is important to review strategies for improving outcomes following ASCT. Conditioning prior to ASCT with higher doses of melphalan, and combinations of melphalan with other agents, including radiopharmaceuticals have been explored. Tandem ASCT, consolidation and maintenance therapy following ASCT have been investigated in phase III trials. Experimental cellular therapies using ex vivo primed dendritic cells , ex vivo expanded autologous lymphocytes, KIR-mismatched allogeneic NK cells, and genetically modified T cells are also in phase I trials to augment ASCT. This review summarises these strategies and highlights the importance of exploring strategies to augment ASCT even in the era of novel agent induction.

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Bortezomib Plus Dexamethasone Is Superior to Vincristine Plus Doxorubicin Plus Dexamethasone As Induction Treatment Prior to Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: Results of the IFM 2005-01 Phase III Trial

Abstract: Bortezomib plus dexamethasone significantly improved postinduction and post-transplantation CR/nCR and at least VGPR rates compared with VAD and resulted in a trend for longer PFS. Bortezomib plus dexamethasone should therefore be considered a standard of care in this setting.

Cited by 502 publications

References 42 publications

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

Growth factor plus preemptive (‘just-in-time’) plerixafor successfully mobilizes hematopoietic stem cells in multiple myeloma patients despite prior lenalidomide exposure

Augmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma

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