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Philippe Moreau - One of the best experts on this subject based on the ideXlab platform.
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bortezomib thalidomide and dexamethasone with or without daratumumab before and after autologous stem cell transplantation for newly diagnosed multiple Myeloma cassiopeia a randomised open label phase 3 study
The Lancet, 2019Co-Authors: Philippe Moreau, Michel Attal, Cyrille Hulin, Bertrand Arnulf, Karim Belhadj, Lotfi Benboubker, Marie C Bene, Annemiek Broijl, Helene Caillon, Denis CaillotAbstract:Summary Background Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple Myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple Myeloma. Methods In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple Myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Findings Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10−5 sensitivity threshold, assessed by multiparametric flow cytometry; both p Interpretation D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple Myeloma. Funding The Intergroupe Francophone du Myelome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
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bortezomib thalidomide and dexamethasone with or without daratumumab before and after autologous stem cell transplantation for newly diagnosed multiple Myeloma cassiopeia a randomised open label phase 3 study
The Lancet, 2019Co-Authors: Philippe Moreau, Michel Attal, Cyrille Hulin, Bertrand Arnulf, Karim Belhadj, Lotfi Benboubker, Marie C Bene, Annemiek Broijl, Helene Caillon, Denis CaillotAbstract:Summary Background Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple Myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple Myeloma. Methods In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple Myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Findings Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10−5 sensitivity threshold, assessed by multiparametric flow cytometry; both p Interpretation D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple Myeloma. Funding The Intergroupe Francophone du Myelome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
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front line transplantation program with lenalidomide bortezomib and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple Myeloma a phase ii study by the intergroupe francophone du myelome
Journal of Clinical Oncology, 2014Co-Authors: Murielle Roussel, Cyrille Hulin, Philippe Moreau, Gerald Marit, Lotfi Benboubker, Valerie Lauwerscances, Nelly Robillard, Xavier Leleu, Brigitte Pegourie, Denis CaillotAbstract:Purpose The three-drug combination of lenalidomide, bortezomib, and dexamethasone (RVD) has shown significant efficacy in multiple Myeloma (MM). The Intergroupe Francophone du Myelome (IFM) decided to evaluate RVD induction and consolidation therapies in a sequential intensive strategy for previously untreated transplantation-eligible patients with MM. Patients and Methods In this phase II study, 31 symptomatic patients age < 65 years were enrolled to receive three RVD induction cycles followed by cyclophosphamide harvest and transplantation. Patients subsequently received two RVD consolidation cycles and 1-year lenalidomide maintenance. Results Very good partial response rate or better at the completion of induction, transplantation, and consolidation therapy was 58%, 70%, and 87%, respectively. Maintenance upgraded responses in 27% of patients. Overall, 58% of patients achieved complete response, and 68% were minimal residual disease (MRD) negative by flow cytometry. The most common toxicities with RVD ...
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combination of international scoring system 3 high lactate dehydrogenase and t 4 14 and or del 17p identifies patients with multiple Myeloma mm treated with front line autologous stem cell transplantation at high risk of early mm progression related death
Journal of Clinical Oncology, 2014Co-Authors: Philippe Moreau, Michel Attal, Michele Cavo, Pieter Sonneveld, Laura Rosinol, Annalisa Pezzi, Hartmut Goldschmidt, Juan Jose Lahuerta, Gerald Marit, Antonio PalumboAbstract:Purpose To construct and validate among patients with multiple Myeloma (MM) who were treated with intensive therapy a prognostic index of early MM progression–related death. Patients and Methods Patient-level data from the Intergroupe Francophone du Myelome (IFM) 2005-01 trial (N = 482) were used to construct the prognostic index. The event was MM progression–related death within 2 years from treatment initiation. The index was validated using data from three other trials: the Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) 26866138-MMY-3006 trial (N = 480), the Programa para el Estudio de la Terapeutica en Hemopatia Maligna (PETHEMA)–GEMMENOS65 trial (N = 390), and the Hemato-Oncologie voor Volwassenen Nederland (HOVON) –65/German-Speaking Myeloma Multicenter Group (GMMG) –HD4 trial (N = 827). Results The risk of early MM progression–related death was related to three independent prognostic variables: lactate dehydrogenase (LDH) higher than than normal, International Staging System 3 (ISS3), ...
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long term follow up of autotransplantation trials for multiple Myeloma update of protocols conducted by the intergroupe francophone du myelome southwest oncology group and university of arkansas for medical sciences
Journal of Clinical Oncology, 2010Co-Authors: Bart Barlogie, Michel Attal, Philippe Moreau, John Crowley, Frits Van Rhee, Jackie Szymonifka, Brian G M Durie, Jeanluc HarousseauAbstract:Purpose The purpose of this study was to update outcomes of autotransplantation trials for Myeloma conducted by the Intergroupe Francophone du Myelome (IFM), the Southwest Oncology Group, and the University of Arkansas for Medical Sciences (Total Therapy [TT]). Methods IFM90 (N = 194), IFM04 (N = 402), IFM9902 (N = 692), IFM9904 (N = 197), S9321 (N = 817), TT1 (N = 231), TT2 (N = 668), and TT3 (N = 303) were updated, and results were compared with original reports. Results Superior survival with single transplantation versus standard therapy in IFM90 was confirmed (P = .004), and a trend in favor of tandem versus single transplantation was maintained in IFM94 (P = .08). S9321 data were validated, with comparable survival in single transplantation and standard treatment arms (P = .35). A survival benefit from thalidomide maintenance in IFM9902 was not confirmed (P = .39) but emerged for the thalidomide arm of TT2 (P = .04). On multivariate analysis, survival was superior in TT2, TT3, and IFM9902 (all P < ....
Michel Attal - One of the best experts on this subject based on the ideXlab platform.
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bortezomib thalidomide and dexamethasone with or without daratumumab before and after autologous stem cell transplantation for newly diagnosed multiple Myeloma cassiopeia a randomised open label phase 3 study
The Lancet, 2019Co-Authors: Philippe Moreau, Michel Attal, Cyrille Hulin, Bertrand Arnulf, Karim Belhadj, Lotfi Benboubker, Marie C Bene, Annemiek Broijl, Helene Caillon, Denis CaillotAbstract:Summary Background Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple Myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple Myeloma. Methods In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple Myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Findings Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10−5 sensitivity threshold, assessed by multiparametric flow cytometry; both p Interpretation D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple Myeloma. Funding The Intergroupe Francophone du Myelome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
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bortezomib thalidomide and dexamethasone with or without daratumumab before and after autologous stem cell transplantation for newly diagnosed multiple Myeloma cassiopeia a randomised open label phase 3 study
The Lancet, 2019Co-Authors: Philippe Moreau, Michel Attal, Cyrille Hulin, Bertrand Arnulf, Karim Belhadj, Lotfi Benboubker, Marie C Bene, Annemiek Broijl, Helene Caillon, Denis CaillotAbstract:Summary Background Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple Myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple Myeloma. Methods In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple Myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Findings Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10−5 sensitivity threshold, assessed by multiparametric flow cytometry; both p Interpretation D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple Myeloma. Funding The Intergroupe Francophone du Myelome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
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combination of international scoring system 3 high lactate dehydrogenase and t 4 14 and or del 17p identifies patients with multiple Myeloma mm treated with front line autologous stem cell transplantation at high risk of early mm progression related death
Journal of Clinical Oncology, 2014Co-Authors: Philippe Moreau, Michel Attal, Michele Cavo, Pieter Sonneveld, Laura Rosinol, Annalisa Pezzi, Hartmut Goldschmidt, Juan Jose Lahuerta, Gerald Marit, Antonio PalumboAbstract:Purpose To construct and validate among patients with multiple Myeloma (MM) who were treated with intensive therapy a prognostic index of early MM progression–related death. Patients and Methods Patient-level data from the Intergroupe Francophone du Myelome (IFM) 2005-01 trial (N = 482) were used to construct the prognostic index. The event was MM progression–related death within 2 years from treatment initiation. The index was validated using data from three other trials: the Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) 26866138-MMY-3006 trial (N = 480), the Programa para el Estudio de la Terapeutica en Hemopatia Maligna (PETHEMA)–GEMMENOS65 trial (N = 390), and the Hemato-Oncologie voor Volwassenen Nederland (HOVON) –65/German-Speaking Myeloma Multicenter Group (GMMG) –HD4 trial (N = 827). Results The risk of early MM progression–related death was related to three independent prognostic variables: lactate dehydrogenase (LDH) higher than than normal, International Staging System 3 (ISS3), ...
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long term follow up of autotransplantation trials for multiple Myeloma update of protocols conducted by the intergroupe francophone du myelome southwest oncology group and university of arkansas for medical sciences
Journal of Clinical Oncology, 2010Co-Authors: Bart Barlogie, Michel Attal, Philippe Moreau, John Crowley, Frits Van Rhee, Jackie Szymonifka, Brian G M Durie, Jeanluc HarousseauAbstract:Purpose The purpose of this study was to update outcomes of autotransplantation trials for Myeloma conducted by the Intergroupe Francophone du Myelome (IFM), the Southwest Oncology Group, and the University of Arkansas for Medical Sciences (Total Therapy [TT]). Methods IFM90 (N = 194), IFM04 (N = 402), IFM9902 (N = 692), IFM9904 (N = 197), S9321 (N = 817), TT1 (N = 231), TT2 (N = 668), and TT3 (N = 303) were updated, and results were compared with original reports. Results Superior survival with single transplantation versus standard therapy in IFM90 was confirmed (P = .004), and a trend in favor of tandem versus single transplantation was maintained in IFM94 (P = .08). S9321 data were validated, with comparable survival in single transplantation and standard treatment arms (P = .35). A survival benefit from thalidomide maintenance in IFM9902 was not confirmed (P = .39) but emerged for the thalidomide arm of TT2 (P = .04). On multivariate analysis, survival was superior in TT2, TT3, and IFM9902 (all P < ....
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genetic abnormalities and survival in multiple Myeloma the experience of the intergroupe francophone du myelome
Blood, 2007Co-Authors: Herve Avetloiseau, Frederic Garban, Mauricette Michallet, Ibrahim Yakoubagha, Catherine Charbonnel, Michel Attal, Serge Leyvraz, Cyrille Hulin, Philippe Moreau, Laurent GarderetAbstract:Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic Myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myelome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In Myeloma, the genomic aberrations t(4;14) and del(17p), together with β2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.
Denis Caillot - One of the best experts on this subject based on the ideXlab platform.
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bortezomib thalidomide and dexamethasone with or without daratumumab before and after autologous stem cell transplantation for newly diagnosed multiple Myeloma cassiopeia a randomised open label phase 3 study
The Lancet, 2019Co-Authors: Philippe Moreau, Michel Attal, Cyrille Hulin, Bertrand Arnulf, Karim Belhadj, Lotfi Benboubker, Marie C Bene, Annemiek Broijl, Helene Caillon, Denis CaillotAbstract:Summary Background Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple Myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple Myeloma. Methods In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple Myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Findings Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10−5 sensitivity threshold, assessed by multiparametric flow cytometry; both p Interpretation D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple Myeloma. Funding The Intergroupe Francophone du Myelome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
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bortezomib thalidomide and dexamethasone with or without daratumumab before and after autologous stem cell transplantation for newly diagnosed multiple Myeloma cassiopeia a randomised open label phase 3 study
The Lancet, 2019Co-Authors: Philippe Moreau, Michel Attal, Cyrille Hulin, Bertrand Arnulf, Karim Belhadj, Lotfi Benboubker, Marie C Bene, Annemiek Broijl, Helene Caillon, Denis CaillotAbstract:Summary Background Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple Myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple Myeloma. Methods In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple Myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Findings Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10−5 sensitivity threshold, assessed by multiparametric flow cytometry; both p Interpretation D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple Myeloma. Funding The Intergroupe Francophone du Myelome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
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lenalidomide maintenance after autologous stem cell transplantation in newly diagnosed multiple Myeloma a meta analysis
Journal of Clinical Oncology, 2017Co-Authors: Philip L Mccarthy, Cyrille Hulin, Sarah A Holstein, Maria Teresa Petrucci, Paul G Richardson, Patrizia Tosi, Sara Bringhen, Pellegrino Musto, Kenneth C Anderson, Denis CaillotAbstract:PurposeLenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple Myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting.Patients and MethodsThe meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Myelome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for pri...
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front line transplantation program with lenalidomide bortezomib and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple Myeloma a phase ii study by the intergroupe francophone du myelome
Journal of Clinical Oncology, 2014Co-Authors: Murielle Roussel, Cyrille Hulin, Philippe Moreau, Gerald Marit, Lotfi Benboubker, Valerie Lauwerscances, Nelly Robillard, Xavier Leleu, Brigitte Pegourie, Denis CaillotAbstract:Purpose The three-drug combination of lenalidomide, bortezomib, and dexamethasone (RVD) has shown significant efficacy in multiple Myeloma (MM). The Intergroupe Francophone du Myelome (IFM) decided to evaluate RVD induction and consolidation therapies in a sequential intensive strategy for previously untreated transplantation-eligible patients with MM. Patients and Methods In this phase II study, 31 symptomatic patients age < 65 years were enrolled to receive three RVD induction cycles followed by cyclophosphamide harvest and transplantation. Patients subsequently received two RVD consolidation cycles and 1-year lenalidomide maintenance. Results Very good partial response rate or better at the completion of induction, transplantation, and consolidation therapy was 58%, 70%, and 87%, respectively. Maintenance upgraded responses in 27% of patients. Overall, 58% of patients achieved complete response, and 68% were minimal residual disease (MRD) negative by flow cytometry. The most common toxicities with RVD ...
Cyrille Hulin - One of the best experts on this subject based on the ideXlab platform.
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bortezomib thalidomide and dexamethasone with or without daratumumab before and after autologous stem cell transplantation for newly diagnosed multiple Myeloma cassiopeia a randomised open label phase 3 study
The Lancet, 2019Co-Authors: Philippe Moreau, Michel Attal, Cyrille Hulin, Bertrand Arnulf, Karim Belhadj, Lotfi Benboubker, Marie C Bene, Annemiek Broijl, Helene Caillon, Denis CaillotAbstract:Summary Background Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple Myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple Myeloma. Methods In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple Myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Findings Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10−5 sensitivity threshold, assessed by multiparametric flow cytometry; both p Interpretation D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple Myeloma. Funding The Intergroupe Francophone du Myelome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
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bortezomib thalidomide and dexamethasone with or without daratumumab before and after autologous stem cell transplantation for newly diagnosed multiple Myeloma cassiopeia a randomised open label phase 3 study
The Lancet, 2019Co-Authors: Philippe Moreau, Michel Attal, Cyrille Hulin, Bertrand Arnulf, Karim Belhadj, Lotfi Benboubker, Marie C Bene, Annemiek Broijl, Helene Caillon, Denis CaillotAbstract:Summary Background Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple Myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple Myeloma. Methods In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple Myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Findings Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10−5 sensitivity threshold, assessed by multiparametric flow cytometry; both p Interpretation D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple Myeloma. Funding The Intergroupe Francophone du Myelome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
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lenalidomide maintenance after autologous stem cell transplantation in newly diagnosed multiple Myeloma a meta analysis
Journal of Clinical Oncology, 2017Co-Authors: Philip L Mccarthy, Cyrille Hulin, Sarah A Holstein, Maria Teresa Petrucci, Paul G Richardson, Patrizia Tosi, Sara Bringhen, Pellegrino Musto, Kenneth C Anderson, Denis CaillotAbstract:PurposeLenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple Myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting.Patients and MethodsThe meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Myelome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for pri...
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front line transplantation program with lenalidomide bortezomib and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple Myeloma a phase ii study by the intergroupe francophone du myelome
Journal of Clinical Oncology, 2014Co-Authors: Murielle Roussel, Cyrille Hulin, Philippe Moreau, Gerald Marit, Lotfi Benboubker, Valerie Lauwerscances, Nelly Robillard, Xavier Leleu, Brigitte Pegourie, Denis CaillotAbstract:Purpose The three-drug combination of lenalidomide, bortezomib, and dexamethasone (RVD) has shown significant efficacy in multiple Myeloma (MM). The Intergroupe Francophone du Myelome (IFM) decided to evaluate RVD induction and consolidation therapies in a sequential intensive strategy for previously untreated transplantation-eligible patients with MM. Patients and Methods In this phase II study, 31 symptomatic patients age < 65 years were enrolled to receive three RVD induction cycles followed by cyclophosphamide harvest and transplantation. Patients subsequently received two RVD consolidation cycles and 1-year lenalidomide maintenance. Results Very good partial response rate or better at the completion of induction, transplantation, and consolidation therapy was 58%, 70%, and 87%, respectively. Maintenance upgraded responses in 27% of patients. Overall, 58% of patients achieved complete response, and 68% were minimal residual disease (MRD) negative by flow cytometry. The most common toxicities with RVD ...
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genetic abnormalities and survival in multiple Myeloma the experience of the intergroupe francophone du myelome
Blood, 2007Co-Authors: Herve Avetloiseau, Frederic Garban, Mauricette Michallet, Ibrahim Yakoubagha, Catherine Charbonnel, Michel Attal, Serge Leyvraz, Cyrille Hulin, Philippe Moreau, Laurent GarderetAbstract:Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic Myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myelome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In Myeloma, the genomic aberrations t(4;14) and del(17p), together with β2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.
Faith E Davies - One of the best experts on this subject based on the ideXlab platform.
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the requirement for dnam 1 nkg2d and nkp46 in the natural killer cell mediated killing of Myeloma cells
Cancer Research, 2007Co-Authors: Yasser M Elsherbiny, Josephine L Meade, Tim D Holmes, Dennis Mcgonagle, Sarah L Mackie, Ann W Morgan, Gordon Cook, Sylvia Feyler, Stephen J Richards, Faith E DaviesAbstract:Recent evidence suggests a role for natural killer (NK) cells in the control of multiple Myeloma. We show that expression of the NK cell receptor DNAM-1 (CD226) is reduced on CD56(dim) NK cells from Myeloma patients with active disease compared with patients in remission and healthy controls. This suggested that this receptor might play a role in NK-Myeloma interactions. The DNAM-1 ligands Nectin-2 (CD112) and the poliovirus receptor (PVR; CD155) were expressed by most patient Myeloma samples analyzed. NK killing of patient-derived Myelomas expressing PVR and/or Nectin-2 was DNAM-1 dependent, revealing a functional role for DNAM-1 in Myeloma cell killing. In Myeloma cell lines, cell surface expression of PVR was associated with low levels of NKG2D ligands, whereas cells expressing high levels of NKG2D ligands did not express PVR protein or mRNA. Furthermore, NK cell-mediated killing of Myeloma cell lines was dependent on either DNAM-1 or NKG2D but not both molecules. In contrast, the natural cytotoxicity receptor NKp46 was required for the killing of all Myeloma cell lines analyzed. Thus, DNAM-1 is important in the NK cell-mediated killing of Myeloma cells expressing the cognate ligands. The importance of NKp46, NKG2D, and DNAM-1 in Myeloma killing mirrors the differential expression of NK cell ligands by Myeloma cells, reflecting immune selection during Myeloma disease progression.
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the requirement for dnam 1 nkg2d and nkp46 in the natural killer cell mediated killing of Myeloma cells
Cancer Research, 2007Co-Authors: Yasser M Elsherbiny, Josephine L Meade, Tim D Holmes, Dennis Mcgonagle, Sarah L Mackie, Ann W Morgan, Gordon Cook, Sylvia Feyler, Stephen J Richards, Faith E DaviesAbstract:Recent evidence suggests a role for natural killer (NK) cells in the control of multiple Myeloma. We show that expression of the NK cell receptor DNAM-1 (CD226) is reduced on CD56dim NK cells from Myeloma patients with active disease compared with patients in remission and healthy controls. This suggested that this receptor might play a role in NK-Myeloma interactions. The DNAM-1 ligands Nectin-2 (CD112) and the poliovirus receptor (PVR; CD155) were expressed by most patient Myeloma samples analyzed. NK killing of patient-derived Myelomas expressing PVR and/or Nectin-2 was DNAM-1 dependent, revealing a functional role for DNAM-1 in Myeloma cell killing. In Myeloma cell lines, cell surface expression of PVR was associated with low levels of NKG2D ligands, whereas cells expressing high levels of NKG2D ligands did not express PVR protein or mRNA. Furthermore, NK cell-mediated killing of Myeloma cell lines was dependent on either DNAM-1 or NKG2D but not both molecules. In contrast, the natural cytotoxicity receptor NKp46 was required for the killing of all Myeloma cell lines analyzed. Thus, DNAM-1 is important in the NK cell-mediated killing of Myeloma cells expressing the cognate ligands. The importance of NKp46, NKG2D, and DNAM-1 in Myeloma killing mirrors the differential expression of NK cell ligands by Myeloma cells, reflecting immune selection during Myeloma disease progression. [Cancer Res 2007;67(18):8444–9]
