Murielle Roussel1, Valérie Lauwers-Cances2, Nelly Robillard2, Cyrille Hulin2, Xavier Leleu2, Lotfi Benboubker2, Gérald Marit2, Philippe Moreau2, Brigitte Pegourie2, Denis Caillot2, Christophe Fruchart2, Anne-Marie Stoppa2, Catherine Gentil2, Soraya Wuilleme2, Anne Huynh2, Benjamin Hebraud2, Jill Corre2, Marie-Lorraine Chretien2, Thierry Facon2, Hervé Avet-Loiseau2, Michel Attal2. 1. Murielle Roussel, Valérie Lauwers-Cances, Catherine Gentil, Anne Huynh, Benjamin Hebraud, Jill Corre, and Hervé Avet-Loiseau, Hopitaux de Toulouse; Michel Attal, Institut Claudius Regaud, Toulouse; Nelly Robillard, Philippe Moreau, and Soraya Wuilleme, Hôtel Dieu, Nantes; Cyrille Hulin, Centre Hospitalier Brabois, Nancy; Xavier Leleu and Thierry Facon, Hôpital Claude Huriez, Lille; Lotfi Benboubker, Hôpital Bretonneau, Tours; Gérald Marit, Hôpital Haut-Lévêque, Bordeaux Pessac; Brigitte Pegourie, Hôpital Albert Michallon, Grenoble; Denis Caillot and Marie-Lorraine Chretien, Centre Hospitalier Le Bocage, Dijon; Christophe Fruchart, Centre François Baclesse, Caen; and Anne-Marie Stoppa, Institut Paoli Calmettes, Marseille, France. roussel.m@chu-toulouse.fr. 2. Murielle Roussel, Valérie Lauwers-Cances, Catherine Gentil, Anne Huynh, Benjamin Hebraud, Jill Corre, and Hervé Avet-Loiseau, Hopitaux de Toulouse; Michel Attal, Institut Claudius Regaud, Toulouse; Nelly Robillard, Philippe Moreau, and Soraya Wuilleme, Hôtel Dieu, Nantes; Cyrille Hulin, Centre Hospitalier Brabois, Nancy; Xavier Leleu and Thierry Facon, Hôpital Claude Huriez, Lille; Lotfi Benboubker, Hôpital Bretonneau, Tours; Gérald Marit, Hôpital Haut-Lévêque, Bordeaux Pessac; Brigitte Pegourie, Hôpital Albert Michallon, Grenoble; Denis Caillot and Marie-Lorraine Chretien, Centre Hospitalier Le Bocage, Dijon; Christophe Fruchart, Centre François Baclesse, Caen; and Anne-Marie Stoppa, Institut Paoli Calmettes, Marseille, France.
Abstract
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. 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 were neurologic and hematologic, including grade 1 to 2 sensory neuropathy (55%), grade 3 to 4 neutropenia (35%), and thrombocytopenia (13%). Two basal cell carcinomas in the same patient and one case of breast cancer were observed. There was no treatment-related mortality. With a median follow-up of 39 months, estimated 3-year progression-free and overall survival were 77% and 100%, respectively. None of the patients who achieved MRD negativity relapsed. CONCLUSION: The transplantation program with RVD induction and consolidation followed by lenalidomide maintenance produced high-quality responses and showed favorable tolerability in patients with newly diagnosed MM. Overall, 68% of patients achieved MRD negativity; none of these patients relapsed. This program is being evaluated in the ongoing IFM/Dana-Farber Cancer Institute 2009 phase III study.
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. 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 were neurologic and hematologic, including grade 1 to 2 sensory neuropathy (55%), grade 3 to 4 neutropenia (35%), and thrombocytopenia (13%). Two basal cell carcinomas in the same patient and one case of breast cancer were observed. There was no treatment-related mortality. With a median follow-up of 39 months, estimated 3-year progression-free and overall survival were 77% and 100%, respectively. None of the patients who achieved MRD negativity relapsed. CONCLUSION: The transplantation program with RVD induction and consolidation followed by lenalidomide maintenance produced high-quality responses and showed favorable tolerability in patients with newly diagnosed MM. Overall, 68% of patients achieved MRD negativity; none of these patients relapsed. This program is being evaluated in the ongoing IFM/Dana-Farber Cancer Institute 2009 phase III study.
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