Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study

Cavo, Michèle; Tacchetti, Paola; Patriarca, Francesca; Petrucci, Maria Teresa; Pantani, Lucia; Galli, Mónica; Raimondo, Francesco Di; Crippa, Claudia; Zamagni, Elena; Palumbo, Antônio; Offidani, Massimo; Corradini, Paolo; Narni, Franco; Spadano, Antonio; Pescosta, Norbert; Deliliers, Giorgio Lambertenghi; Ledda, Antonio; Cellini, Claudia; Caravita, Tommaso; Tosi, Patrizia; Baccarani, Michele

doi:10.1016/s0140-6736(10)61424-9

Cited by 771 publications

(639 citation statements)

References 35 publications

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“…In randomized trials, VTD has shown better response rates and PFS compared with TD [58], as well as VD [59]. Results from randomized trials are not available for VRD and VCD, and the use of these two regimens in clinical practice is driven by promising results from Phase II studies.…”

Section: Risk-adapted Therapymentioning

confidence: 99%

“…There are no data on whether these regimens are superior to Rd in terms of OS, and no data comparing the quality of life across the various combinations that can be used in initial therapy. However, bortezomib-containing regimens appear to overcome the poor prognosis associated with the t4;14 translocation, and certain other cytogenetic abnormalities [58,[62][63][64].…”

Section: Risk-adapted Therapymentioning

confidence: 99%

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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%

Section: Risk-adapted Therapymentioning

confidence: 99%

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

2013

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“…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). Combining lenalidomide with bortezomib plus dexamethasone produced an ORR of 94% in a phase II IFM study (Roussel et al, 2014).…”

Section: Novel Agent Inductionmentioning

confidence: 99%

“…In a phase III trial of adding bortezomib to thalidomide and dexamethasone (i.e. VTD vs TD) for both induction and consolidation, there was no overall survival benefit, but 3-year progression free survival increased from 56% to 68% commensurate with deepening response (Cavo et al, 2010). The consistent finding of deeper responses with delayed progression but no effect on overall survival likely reflects more effective salvage treatment at relapse for the control group.…”

Section: Consolidationmentioning

confidence: 99%

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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“…However, with newer treatment approaches, we can achieve CR in a large majority of patients, including a significant proportion with stringent CR representing lack of clonal plasma cells in the marrow by immunophenotyping. [5][6][7] Despite this level of response, studies have shown that the vast majority of patients have residual tumor cells that can be detected with a variety of sensitive techniques. [8][9][10][11] Several studies have demonstrated a consistent improvement in progression-free survival (PFS) with attainment of CR, but its impact on overall survival (OS) has been varied.…”

mentioning

confidence: 99%