Originally published as JCO Early Release 10.1200/JCO.2008.21.0948 on May 18 2009

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Efficacy of Melphalan and Prednisone Plus Thalidomide in Patients Older Than 75 Years With Newly Diagnosed Multiple Myeloma: IFM 01/01 Trial

From the Centre Hospitalier Universitaire, Nancy; Centre Hospitalier Universitaire, Lille; Centre Hospitalier, Blois; Centre Hospitalier Universitaire, Grenoble; Centre Hospitalier Universitaire, Tours; Centre Hospitalier Universitaire, Angers; Centre Hospitalier Universitaire, Brest; Centre Hospitalier Chalon sur Saône; Centre Hospitalier Universitaire, Reims; Centre Henri Becquerel, Rouen; Centre Hospitalier Universitaire, Bobigny; Centre Hospitalier Universitaire, Poitiers; Centre Hospitalier Universitaire, Rennes; Centre Hospitalier Universitaire Saint-Antoine; Institut Curie, Paris; Centre Hospitalier Universitaire Besancon; Centre Hospitalier Universitaire, Dijon; Centre Hospitalier Universitaire, Nantes, France; and the Cliniques Universitaire de Mont-Godinne, Yvoir, Belgium.

Corresponding author: Cyrille Hulin, MD, Service d'Hématologie, rue du Morvan, Centre Hospitalier Universitaire de Nancy–Brabois, 54511 Vandoeuvre, France; e-mail: c.hulin{at}chu-nancy.fr.

Purpose Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma.

Patients and Methods Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival.

Results After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003).

Conclusion This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.

Written on behalf of the Intergroupe Francophone du Myelome.

Sponsored by the Centre Hospitalier Universitaire de Nancy; by a research grant from the French Ministry of Health (Projet Hospitalier de Recherche Clinique, CHRU Nancy 2001, No. 04.9702); by Laphal; by Pharmion; and by Celgene, which supplied free experimental treatment (thalidomide or placebo) for the study.

Presented in part in abstract format at the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2007; XIth International Myeloma Workshop, Kos Island, Greece, June 25-30, 2007; and the American Society of Hematology, Atlanta, GA, December 8-11, 2007.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00644306 [ClinicalTrials.gov] .

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