Use of bortezomib to overcome the poor prognosis of t(4;14), but not del(17p), in young patients with newly diagnosed multiple myeloma.

Avet‐Loiseau, Hervé; Moreau, Philippe; Mathiot, Claire; Charbonnel, Catherine; Facon, T.; Attal, M; Hulin, Cyrille; Marit, Gérald; Minvielle, Stéphane; Harousseau, Jean‐Luc; Myalome, Intergroupe Francophone du

doi:10.1200/jco.2010.28.15_suppl.8113

Cited by 9 publications

(9 citation statements)

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“…This detrimental effect of del17p has also been shown in previously treated patients who were treated with RD, 18 RD plus doxorubicin, 19 or in newly diagnosed patients treated with RD 20 or with bortezomib plus dexamethasone. 21 However, it is disappointing the fact that even combinations of the most active novel agents cannot overcome this effect, which is present in about 10% of patients, suggesting that new treatments and innovative approaches are urgently needed.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that bortezomib may be able to overcome the adverse impact of del13q (by FISH) in patients with relapsed or refractory MM in a retrospective analysis of the APEX/SUMMIT trials, 15 whereas bortezomib with dexamethasone could partly overcome the negative impact of t(4;14) in newly diagnosed, autologous stem cell transplantation-eligible patients. 21 Two recent reports suggested that t(4;14) may not be as important in patients with relapsed or refractory MM treated with RD. However, these reports had quite different conclusions about the importance of del13q: Reece et al 18 suggested that RD overcomes the effect of del13q, whereas in the report of Avet-Loiseau et al del13q (by FISH) was an independent poor prognostic factor.…”

Section: Discussionmentioning

confidence: 99%

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Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies

Dimopoulos

Christoulas²,

Migkou³

et al. 2010

Leukemia

107

106

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We prospectively studied the impact of several cytogenetic abnormalities (CAs) in patients with relapsed/refractory myeloma who received lenalidomide and dexamethasone (RD) with or without the addition of bortezomib (V). On the basis of the presence of previous neuropathy, 50 patients were treated with RD and 49, without preexisting neuropathy, with VRD. The overall response rate was 63%, similar for RD and VRD. Poor risk cytogenetics were associated with lower response rates in RD (P ¼ 0.01), but not in VRD (P ¼ 0.219). The median progression-free survival (PFS) was similar for RD (9 months) and VRD (7 months). The median overall survival (OS) for all patients was 16 months, with no differences between RD or VRD regimens. Poor risk cytogenetics, especially del17p, resistance to previous thalidomide, elevated lactate dehydrogenase (LDH) and presence of extramedullary disease were associated with inferior response to therapy and shorter PFS and OS. The impact of other CAs on OS was more pronounced in RD. In conclusion, the presence of CAs is an important adverse prognostic factor for patients with relapsed/refractory myeloma, but resistance to previous thalidomide, elevated LDH and presence of extramedullary disease remain of major prognostic importance. The outcome of patients with del17p remains extremely poor even with VRD combination.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies

Dimopoulos

Christoulas²,

Migkou³

et al. 2010

Leukemia

107

106

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“…Treatment with bortezomib or lenalidomide containing regimen seems to at least lessen the negative prognostic impact of this aberration (6,(42)(43)(44)(45) and can thus be selected. t(4;14) is present in 13% of patients in our reference cohort and can be predicted without error by GEP (Supplementary Table S2C).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling in Multiple Myeloma—Reporting of Entities, Risk, and Targets in Clinical Routine

Meißner

Seckinger

Rème

et al. 2011

Clinical Cancer Research

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Purpose: Multiple myeloma is an incurable malignant plasma cell disease characterized by survival ranging from several months to more than 15 years. Assessment of risk and underlying molecular heterogeneity can be excellently done by gene expression profiling (GEP), but its way into clinical routine is hampered by the lack of an appropriate reporting tool and the integration with other prognostic factors into a single "meta" risk stratification.Experimental Design: The GEP-report (GEP-R) was built as an open-source software developed in R for gene expression reporting in clinical practice using Affymetrix microarrays. GEP-R processes new samples by applying a documentation-by-value strategy to the raw data to be able to assign thresholds and grouping algorithms defined on a reference cohort of 262 patients with multiple myeloma. Furthermore, we integrated expression-based and conventional prognostic factors within one risk stratification (HM-metascore).Results: The GEP-R comprises (i) quality control, (ii) sample identity control, (iii) biologic classification, (iv) risk stratification, and (v) assessment of target genes. The resulting HM-metascore is defined as the sum over the weighted factors gene expression-based risk-assessment (UAMS-, IFM-score), proliferation, International Staging System (ISS) stage, t(4;14), and expression of prognostic target genes (AURKA, IGF1R) for which clinical grade inhibitors exist. The HM-score delineates three significantly different groups of 13.1%, 72.1%, and 14.7% of patients with a 6-year survival rate of 89.3%, 60.6%, and 18.6%, respectively.Conclusion: GEP reporting allows prospective assessment of risk and target gene expression and integration of current prognostic factors in clinical routine, being customizable about novel parameters or other cancer entities. Clin Cancer Res; 17(23); 7240-7. Ó2011 AACR.

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“…The publications related to the main studies contributed information about extended follow-up of the original studies 33,45,49,53 , subgroup analyses 34,[39][40][41][42][43][44]48,51,52,55,57,59 , health-related qol 36,47,56,76 , outcome data that were not reported in the original publication 35,37,46,49,54,60,61,64,68,74,78 , and data on toxicity 38,50,62 .…”

Section: Literature Searchmentioning

confidence: 99%

Bortezomib in Multiple Myeloma: Systematic Review and Clinical Considerations

Kouroukis

Baldassarre²,

Haynes³

et al. 2014

Current Oncology

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We conducted a systematic review to determine the appropriate use of bortezomib alone or in combination with other agents in patients with multiple myeloma (MM). We searched MEDLINE, EMBASE, the Cochrane Library, conference proceedings, and the reference lists of included studies. We analyzed randomized controlled trials and systematic reviews if they involved adult MM patients treated with bortezomib and if they reported on survival, disease control, response, quality of life, or adverse effects. Twenty-six unique studies met the inclusion criteria. For patients with previously untreated MM and for candidates for transplantation, we found a statistically significant benefit in time to progression [hazard ratio (HR): 0.48, p < 0.001; and HR: 0.63, p = 0.006, respectively] and a better response with a bortezomib than with a non-bortezomib regimen (p < 0.001). Progression-free survival was longer with bortezomib and thalidomide than with thalidomide alone (p = 0.01). In non-candidates for transplantation, a significant benefit in overall survival was observed with a bortezomib regimen (HR compared with a non-bortezomib regimen: 0.61; p = 0.008), and in transplantation candidates receiving bortezomib, the response rate was improved after induction (p = 0.004) and after a first transplant (p = 0.016). In relapsed or refractory MM, overall survival (p = 0.03), time to progression (HR: 1.82; p = 0.000004), and progression-free survival (HR: 1.69; p = 0.000026) were significantly improved with bortezomib and pegylated liposomal doxorubicin (compared with bortezomib alone), and bortezomib monotherapy was better than dexamethasone alone (HR: 0.77; p = 0.027). Bortezomib combined with thalidomide and dexamethasone was better than either bortezomib monotherapy or thalidomide with dexamethasone (p < 0.001). In previously untreated or in relapsed or refractory MM patients, bortezomib-based therapy has

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Use of bortezomib to overcome the poor prognosis of t(4;14), but not del(17p), in young patients with newly diagnosed multiple myeloma.

Cited by 9 publications

References 0 publications

Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies

Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies

Gene Expression Profiling in Multiple Myeloma—Reporting of Entities, Risk, and Targets in Clinical Routine

Bortezomib in Multiple Myeloma: Systematic Review and Clinical Considerations

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