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Multiple Myelom

Philip L McCarthy, Sarah A Holstein, Maria Teresa Petrucci, Paul G Richardson, Cyrille Hulin, Patrizia Tosi, Sara Bringhen, Pellegrino Musto, Kenneth C Anderson, Denis Caillot, Francesca Gay, Philippe Moreau, Gerald Marit, Sin-Ho Jung, Zhinuan Yu, Benjamin Winograd, Robert D Knight, Antonio Palumbo, Michel Attal
Purpose Lenalidomide 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 Methods The 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 Myélome 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 primary efficacy analysis...
October 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Jia-Sheng Hu, Xiao Huang, Ying-Dan Huang, Yan-Yan Lu, Quan-Yi Lu
OBJECTIVE: To study the correlation between the excessive activation of Hedgehog signal and the drug resistance of multiple myeloma. METHODS: The resistant cell line RPMI 8226/R of multiple myeloma was established by an ascending concentration gradient method. The experiment consisted of 4 groups: RPMI8226/R, RPMI8226/S, GANT61+RPMI8226/R and GANT61+RPMI8226/S. The CCK-8 (cell counting kit-8) assay was used to detect the cell proliferation inhibition rate in 4 groups; the RT-PCR was used to detect the expression of Gli1, Gli2, Shh, Ihh, Smo and Sufu in the RPMI8226/S and RPMI8226/R cells...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
(no author information available yet)
No abstract text is available yet for this article.
2016: Oncology Research and Treatment
Christian Straka, Peter Liebisch, Hans Salwender, Burkhard Hennemann, Bernd Metzner, Stefan Knop, Sigrid Adler-Reichel, Christian Gerecke, Hannes Wandt, Martin Bentz, Tim Hendrik Bruemmendorf, Marcus Hentrich, Michael Pfreundschuh, Hans-Heinrich Wolf, Orhan Sezer, Ralf Bargou, Wolfram Jung, Lorenz Trümper, Bernd Hertenstein, Else Heidemann, Helga Bernhard, Nicola Lang, Norbert Frickhofen, Holger Hebart, Ralf Schmidmaier, Andreas Sandermann, Tobias Dechow, Albrecht Reichle, Brigitte Schnabel, Kerstin Schäfer-Eckart, Christian Langer, Martin Gramatzki, Axel Hinke, Bertold Emmerich, Hermann Einsele
Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction. For all patients, double autologous transplantation after melphalan 140 mg/m2 (MEL140) was planned. The primary end point was progression-free survival. Of 420 eligible patients, 85% received a first transplant and 69% completed double transplantation...
November 2016: Haematologica
Thomas Dejoie, Daniela Lakomy, Hélène Caillon, Brigitte Pegourié, Olivier Decaux
Serum and urine proteins electrophoresis take a major place in multiple myeloma management, at time of diagnosis, during follow-up for treatment response evaluation and also in detection of relapse. The Intergroupe francophone du myélome (IFM) suggests recommendations to clinicians and biologists, to perform and interpret these biochemical analysis, with the objective of harmonizing practices between laboratories and improving patients' follow-up.
August 1, 2016: Annales de Biologie Clinique
Sarah Keppler, Susann Weiβbach, Christian Langer, Stefan Knop, Jordan Pischimarov, Miriam Kull, Thorsten Stühmer, Torsten Steinbrunn, Ralf Bargou, Hermann Einsele, Andreas Rosenwald, Ellen Leich
Multiple myeloma (MM) is a plasma cell disorder that is characterized by a great genetic heterogeneity. Recent next generation sequencing studies revealed an accumulation of tumor-associated mutations in receptor tyrosine kinases (RTKs) which may also contribute to the activation of survival pathways in MM. To investigate the clinical role of RTK-mutations in MM, we deep-sequenced the coding DNA-sequence of EGFR, EPHA2, ERBB3, IGF1R, NTRK1 and NTRK2 which were previously found to be mutated in MM, in 75 uniformly treated MM patients of the "Deutsche Studiengruppe Multiples Myelom"...
June 21, 2016: Oncotarget
Florence Magrangeas, Rowan Kuiper, Hervé Avet-Loiseau, Wilfried Gouraud, Catherine Guérin-Charbonnel, Ludovic Ferrer, Alexandre Aussem, Haytham Elghazel, Jérôme Suhard, Henri Der Sakissian, Michel Attal, Nikhil C Munshi, Pieter Sonneveld, Charles Dumontet, Philippe Moreau, Mark van Duin, Loïc Campion, Stéphane Minvielle
PURPOSE: Painful peripheral neuropathy is a frequent toxicity associated with bortezomib therapy. This study aimed to identify loci that affect susceptibility to this toxicity. EXPERIMENTAL DESIGN: A genome-wide association study (GWAS) of 370,605 SNPs was performed to identify risk variants for developing severe bortezomib-induced peripheral neuropathy (BiPN) in 469 patients with multiple myeloma who received bortezomib-dexamethasone therapy prior to autologous stem cell in randomized clinical trials of the Intergroupe Francophone du Myelome (IFM) and findings were replicated in 114 patients with multiple myeloma of the HOVON-65/GMMG-HD4 clinical trial...
September 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Philippe Moreau, Cyrille Hulin, Margaret Macro, Denis Caillot, Carine Chaleteix, Murielle Roussel, Laurent Garderet, Bruno Royer, Sabine Brechignac, Mourad Tiab, Mathieu Puyade, Martine Escoffre, Anne-Marie Stoppa, Thierry Facon, Brigitte Pegourie, Driss Chaoui, Arnaud Jaccard, Borhane Slama, Gerald Marit, Karim Laribi, Pascal Godmer, Odile Luycx, Jean-Claude Eisenmann, Olivier Allangba, Mamoun Dib, Carla Araujo, Jean Fontan, Karim Belhadj, Marc Wetterwald, Véronique Dorvaux, Jean-Paul Fermand, Philippe Rodon, Brigitte Kolb, Sylvie Glaisner, Jean-Valere Malfuson, Pascal Lenain, Laetitia Biron, Lucie Planche, Helene Caillon, Herve Avet-Loiseau, Thomas Dejoie, Michel Attal
The Intergroupe Francophone du Myélome conducted a randomized trial to compare bortezomib-thalidomide-dexamethasone (VTD) with bortezomib-cyclophosphamide-dexamethasone (VCD) as induction before high-dose therapy and autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma. Overall, a total of 340 patients were centrally randomly assigned to receive VTD or VCD. After 4 cycles, on an intent-to-treat basis, 66.3% of the patients in the VTD arm achieved at least a very good partial response (primary end point) vs 56...
May 26, 2016: Blood
R Ben Dhia, Y Ben Ariba, N Boussetta, N Ben Abdelha-Fidh, F Ajili, B Louzir, J Labidi, S Othmani
OBJECTIFS: Les atteintes cardiovasculaires représentent la principale cause de mortalité des patients avec insuffisance rénale chronique terminale. La prévalence ainsi que l'évaluation des autres facteurs de risques associés de l'atteinte cardiaque est une étape importante dans la prise en charge des malades en préhémodialyse. L'objectif de notre étude était de décrire les caractéristiques échocardiographiques de la cardiomyopathie urémique. MéTHODES: Notre étude a été menée sur 16 patients hospitalisés entre 2013 et 2014 au service de médecine interne de l'Hôpital Militaire de Tunis colligeant 16 patients ayant eu une échographie cardiaque dans le cadre d'un bilan pré-hémodialyse...
December 2015: Annales de Cardiologie et D'angéiologie
M Bennaceur, F Belabidi, M Riche, F Otmani, M Arrada
OBJECTIFS: HTA et cancer sont deux affections très fréquentes de par le monde, sources d'une morbi-mortalité importantes. De nombreuses études rapportent une forte association entre ces deux affections. L'HTA semble aug-menter l'incidence et la mortalité pour certains cancers : rein, ORL, colon, rectum, poumon, vessie, mélanome. Certains traitements de l'HTA semblent incriminés pour certains types de cancers. Cependant d'éventuels liens physio-pathologiques entres ces deux affections demeurent encore inconnus...
December 2015: Annales de Cardiologie et D'angéiologie
G Fouquet, B Pegourie, M Macro, M O Petillon, L Karlin, D Caillot, M Roussel, B Arnulf, C Mathiot, G Marit, B Kolb, A M Stoppa, S Brechiniac, V Richez, P Rodon, A Banos, M Wetterwald, L Garderet, B Royer, C Hulin, L Benbouker, O Decaux, M Escoffre-Barbe, J P Fermand, M Attal, H Avet-Loiseau, P Moreau, T Facon, X Leleu
BACKGROUND: The IFM2009-02 trial studied pomalidomide (4 mg daily, 21/28 versus 28/28) and dexamethasone in very advanced relapsed or refractory multiple myeloma (RRMM). We observed that 40% of patients had a prolonged progression-free survival (PFS) and subsequently overall survival (OS). We sought to analyze the characteristics of these patients and study the effect of long exposure to pomalidomide. DESIGN: We separated the studied population into two groups: 3 months to 1 year (<1 year) and more than 1 year (≥1 year) of treatment with pomalidomide and dexamethasone based on clinical judgment and historical control studies...
May 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Meletios A Dimopoulos, Matthew C Cheung, Murielle Roussel, Ting Liu, Barbara Gamberi, Brigitte Kolb, H Guenter Derigs, HyeonSeok Eom, Karim Belhadj, Pascal Lenain, Richard Van der Jagt, Sophie Rigaudeau, Mamoun Dib, Rachel Hall, Henry Jardel, Arnaud Jaccard, Axel Tosikyan, Lionel Karlin, William Bensinger, Rik Schots, Nicolas Leupin, Guang Chen, Jennifer Marek, Annette Ervin-Haynes, Thierry Facon
Renal impairment is associated with poor prognosis in myeloma. This analysis of the pivotal phase 3 FIRST trial examined the impact of renally adapted dosing of lenalidomide and dexamethasone on outcomes of patients with different degrees of renal impairment. Transplant-ineligible patients not requiring dialysis were randomized 1:1:1 to receive continuous lenalidomide and dexamethasone until disease progression (n=535) or for 18 cycles (72 weeks; n=541), or melphalan, prednisone, and thalidomide for 12 cycles (72 weeks; n=547)...
March 2016: Haematologica
Philippe Rodon, Cyrille Hulin, Brigitte Pegourie, Mourad Tiab, Bruno Anglaret, Lotfi Benboubker, Henry Jardel, Olivier Decaux, Brigitte Kolb, Murielle Roussel, Laurent Garderet, Xavier Leleu, Olivier Fitoussi, Carine Chaleteix, Philippe Casassus, Pascal Lenain, Bruno Royer, Anne Banos, Riad Benramdane, Pascale Cony-Makhoul, Mamoun Dib, Jean Fontan, Anne-Marie Stoppa, Catherine Traullé, Jean-Pierre Vilque, Marie-Odile Pétillon, Claire Mathiot, Thomas Dejoie, Hervé Avet-Loiseau, Philippe Moreau
No abstract text is available yet for this article.
February 2015: Haematologica
Zdeněk Adam, Marta Krejčí, Luděk Pour, Eva Sevčíková, Andrea Křivanová, Zdeněk Rehák, Renata Koukalová, Zdeňka Cermáková, Jíří Vaníček, Sabina Sevčíková
Presence of monoclonal immunoglobulin in serum or urine is a relatively common event affecting about 3.2 % of people over 50. Isolated increase of only one type of free light chain, either κ or λ, is detected in 0.7-0.8 % of people over 50. Most people with monoclonal immunoglobulin meet the criteria of the so-called "mono-clonal gammopathy of undetermined significance (MGUS)". MGUS is defined by concentration of monoclonal immunoglobulin in serum < 30 g/l, number of plasma cells in the bone marrow < 10 % and the absence of symptoms of multiple myeloma and other lymphoproliferative diseases...
October 2014: Vnitr̆ní Lékar̆ství
Lotfi Benboubker, Meletios A Dimopoulos, Angela Dispenzieri, John Catalano, Andrew R Belch, Michele Cavo, Antonello Pinto, Katja Weisel, Heinz Ludwig, Nizar Bahlis, Anne Banos, Mourad Tiab, Michel Delforge, Jamie Cavenagh, Catarina Geraldes, Je-Jung Lee, Christine Chen, Albert Oriol, Javier de la Rubia, Lugui Qiu, Darrell J White, Daniel Binder, Kenneth Anderson, Jean-Paul Fermand, Philippe Moreau, Michel Attal, Robert Knight, Guang Chen, Jason Van Oostendorp, Christian Jacques, Annette Ervin-Haynes, Hervé Avet-Loiseau, Cyrille Hulin, Thierry Facon
BACKGROUND: The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches. METHODS: We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients)...
September 4, 2014: New England Journal of Medicine
Murielle Roussel, Valérie Lauwers-Cances, Nelly Robillard, Cyrille Hulin, Xavier Leleu, Lotfi Benboubker, Gérald Marit, Philippe Moreau, Brigitte Pegourie, Denis Caillot, Christophe Fruchart, Anne-Marie Stoppa, Catherine Gentil, Soraya Wuilleme, Anne Huynh, Benjamin Hebraud, Jill Corre, Marie-Lorraine Chretien, Thierry Facon, Hervé Avet-Loiseau, Michel Attal
PURPOSE: The three-drug combination of lenalidomide, bortezomib, and dexamethasone (RVD) has shown significant efficacy in multiple myeloma (MM). The Intergroupe Francophone du Myélome (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...
September 1, 2014: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Yan-sheng Wang, Shi-hua Ding, Fan Wu, Zhi-tao Wang, Qiang-sheng Wang
OBJECTIVE: To analyze the efficacy and safety of subcutaneous administration of bortezomib in the treatment of multiple myeloma (MM) patients. METHODS: A total of 26 MM patients were enrolled in this study and treated with BDT (bortezomib-dexamethasone-thalidomide). In the 26 MM patients, 12 patients received subcutaneous administration of Bortezomib while 14 patients received conventional intravenous administration. The outcomes and adverse effects of two groups were retrospectively evaluated and compared...
May 2014: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
Philippe Moreau, Michele Cavo, Pieter Sonneveld, Laura Rosinol, Michel Attal, Annalisa Pezzi, Hartmut Goldschmidt, Juan Jose Lahuerta, Gerald Marit, Antonio Palumbo, Bronno van der Holt, Joan Bladé, Maria Teresa Petrucci, Kai Neben, Jesus san Miguel, Francesca Patriarca, Henk Lokhorst, Elena Zamagni, Cyrille Hulin, Norma Gutierrez, Thierry Facon, Denis Caillot, Lotfi Benboubker, Jean-Luc Harousseau, Xavier Leleu, Hervé Avet-Loiseau, Jean-Yves Mary
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 Myélome (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 Terapéutica en Hemopatía 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)...
July 10, 2014: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Esteban Braggio
Chromosomal abnormalities are well-established biomarkers used in the subclassification and risk stratification of multiple myeloma patients. Patients with t(4;14)(p16;q32) and deletion 17p13 are considered to have a poor prognosis, and do not respond to any of the available therapies. However, most studies of chromosomal abnormalities incidence and risk stratification have been performed in patients younger than 66 years of age; therefore we have very limited data on the elderly population. This study was designed to uncover the incidence and clinical significance of 17p13 and 13q14 deletions and t(4;14) in a large cohort of clinically annotated multiple myeloma patients older than 66 years of age...
December 2013: Future Oncology
Guillemette Fouquet, Stéphanie Tardy, Hélène Demarquette, Sarah Bonnet, Julie Gay, Houria Debarri, Charles Herbaux, Stéphanie Guidez, Jessica Michel, Aurore Perrot, Caroline Serrier, Darko Miljkovic, Hervé Avet Loiseau, Thierry Facon, Cyrille Hulin, Xavier Leleu
BACKGROUND: Lenalidomide in combination with dexamethasone (Len/Dex) is indicated for patients with recurrent/refractory multiple myeloma (RRMM) who were treated with 1 prior therapy until evidence of disease progression. The objective of the current study was to determine the efficacy and safety profile of long-term exposure to Len/Dex. METHODS: A total of 50 patients with RRMM who were treated with long-term Len for ≥ 2 years from 2 Intergroupe Francophone du Myélome (IFM) centers (Lille and Nancy) were included in the current study...
October 15, 2013: Cancer
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