Philippe Moreau1, Michele Cavo2, Pieter Sonneveld2, Laura Rosinol2, Michel Attal2, Annalisa Pezzi2, Hartmut Goldschmidt2, Juan Jose Lahuerta2, Gerald Marit2, Antonio Palumbo2, Bronno van der Holt2, Joan Bladé2, Maria Teresa Petrucci2, Kai Neben2, Jesus san Miguel2, Francesca Patriarca2, Henk Lokhorst2, Elena Zamagni2, Cyrille Hulin2, Norma Gutierrez2, Thierry Facon2, Denis Caillot2, Lotfi Benboubker2, Jean-Luc Harousseau2, Xavier Leleu2, Hervé Avet-Loiseau2, Jean-Yves Mary2. 1. Philippe Moreau, University Hospital Hôtel-Dieu; Jean-Luc Harousseau, Centre Rene Gauducheau, Nantes; Michel Attal, Centre Hospitalier Universitaire (CHU) Toulouse; Hervé Avet-Loiseau, CHU Rangueil, Toulouse; Gerald Marit, University Hospital of Bordeaux, Bordeaux; Cyrille Hulin, CHU Nancy, Nancy; Thierry Facon, Hopital Claude Huriez; Xavier Leleu, University Hospital of Lille, Lille; Denis Caillot, CHU Dijon, Dijon; Lotfi Benboubker, Centre Hospitalier Régional Universitaire Tours, Tours; Jean-Yves Mary, University Hospital Paris Saint-Louis, Paris, France; Michele Cavo, Annalisa Pezzi, and Elena Zamagni, Seràgnoli Institute of Hematology, Bologna; Antonio Palumbo, University of Torino, Torino; Maria Teresa Petrucci, Sapienza University of Rome, Rome; Francesca Patriarca, University Hospital, Udine, Italy; Pieter Sonneveld, Erasmus Medical Center, Rotterdam; Bronno van der Holt, Daniel den Hoed Cancer Center at Erasmus Medical Center, Rotterdam; Henk Lokhorst, University Medical Center Utrecht, Utrecht, the Netherlands; Hartmut Goldschmidt, Universitätsklinikum Heidelberg; Kai Neben, University of Heidelberg, Heidelberg, Germany; Laura Rosinol and Joan Bladé, Hospital Clinic, Barcelona; Juan Jose Lahuerta, Hospital Universitario 12 de Octubre, Madrid; Jesus san Miguel, University of Salamanca; Norma Gutierrez, Hospital Universitario de Salamanca, Salamanca, Spain. philippe.moreau@chu-nantes.fr. 2. Philippe Moreau, University Hospital Hôtel-Dieu; Jean-Luc Harousseau, Centre Rene Gauducheau, Nantes; Michel Attal, Centre Hospitalier Universitaire (CHU) Toulouse; Hervé Avet-Loiseau, CHU Rangueil, Toulouse; Gerald Marit, University Hospital of Bordeaux, Bordeaux; Cyrille Hulin, CHU Nancy, Nancy; Thierry Facon, Hopital Claude Huriez; Xavier Leleu, University Hospital of Lille, Lille; Denis Caillot, CHU Dijon, Dijon; Lotfi Benboubker, Centre Hospitalier Régional Universitaire Tours, Tours; Jean-Yves Mary, University Hospital Paris Saint-Louis, Paris, France; Michele Cavo, Annalisa Pezzi, and Elena Zamagni, Seràgnoli Institute of Hematology, Bologna; Antonio Palumbo, University of Torino, Torino; Maria Teresa Petrucci, Sapienza University of Rome, Rome; Francesca Patriarca, University Hospital, Udine, Italy; Pieter Sonneveld, Erasmus Medical Center, Rotterdam; Bronno van der Holt, Daniel den Hoed Cancer Center at Erasmus Medical Center, Rotterdam; Henk Lokhorst, University Medical Center Utrecht, Utrecht, the Netherlands; Hartmut Goldschmidt, Universitätsklinikum Heidelberg; Kai Neben, University of Heidelberg, Heidelberg, Germany; Laura Rosinol and Joan Bladé, Hospital Clinic, Barcelona; Juan Jose Lahuerta, Hospital Universitario 12 de Octubre, Madrid; Jesus san Miguel, University of Salamanca; Norma Gutierrez, Hospital Universitario de Salamanca, Salamanca, Spain.
Abstract
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). 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), and adverse cytogenetics [t(4;14) and/or del(17p)]. These three variables enabled the definition of an ordinal prognostic classification composed of four scores (0 to 3). Patients with a score of 3, defined by the presence of t(4;14) and/or del(17p) in addition to ISS3 and/or high LDH, comprised 5% (20 of 387 patients) to 8% (94 of 1,139 patients) of the patients in the learning and validation samples, respectively, and they had a very poor prognosis. When applied to the population of 855 patients who had received bortezomib-based induction therapy in the four trials, the prognostic classification was also able to segregate patients into four categories, with a very poor prognosis attributed to patients with a score of 3. CONCLUSION: Our model allows the simple definition of a subgroup of MM patients at high risk of early MM progression-related death despite the use of the most modern and effective strategies.
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). 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), and adverse cytogenetics [t(4;14) and/or del(17p)]. These three variables enabled the definition of an ordinal prognostic classification composed of four scores (0 to 3). Patients with a score of 3, defined by the presence of t(4;14) and/or del(17p) in addition to ISS3 and/or high LDH, comprised 5% (20 of 387 patients) to 8% (94 of 1,139 patients) of the patients in the learning and validation samples, respectively, and they had a very poor prognosis. When applied to the population of 855 patients who had received bortezomib-based induction therapy in the four trials, the prognostic classification was also able to segregate patients into four categories, with a very poor prognosis attributed to patients with a score of 3. CONCLUSION: Our model allows the simple definition of a subgroup of MM patients at high risk of early MM progression-related death despite the use of the most modern and effective strategies.
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