04.07.2006

Blood, 1 May 2006, Vol. 107, No. 9, pp. 3474-3480.
Prepublished online as a Blood First Edition Paper on January 5, 2006; DOI 10.1182/blood-2005-09-3869.

CLINICAL TRIALS AND OBSERVATIONS

Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma

Frederic Garban, Michel Attal, Mauricette Michallet, Cyrille Hulin, Jean H. Bourhis, Ibrahim Yakoub-Agha, Thierry Lamy, Gerald Marit, Frederic Maloisel, Christian Berthou, Mamoun Dib, Denis Caillot, Bernard dePrijck, Nicolas Ketterer, Jean-Luc Harousseau, Jean-Jacques Sotto, Philippe Moreau, for the Intergroupe Francophone du Myélome and the Swiss Group for Clinical Cancer Research
From the University Hospital, Grenoble; University Hospital, Toulouse; University Hospital, Lyon; University Hospital, Nancy; Institut Gustave-Roussy, Paris; University Hospital, Lille; University Hospital, Rennes; University Hospital, Bordeaux; University Hospital, Strasbourg; University Hospital, Brest; University Hospital, Angers; University Hospital, Dijon; University Hospital, Nantes, France; University Hospital, Liège, Belgium; and University Hospital, Lausanne, Switzerland.
The Intergroupe Francophone du Myélome (IFM) initiated 2 trials in 1999 to study patients with high-risk ( 2-microglobulin level greater than 3 mg/L and chromosome 13 deletion at diagnosis) de novo multiple myeloma. In both protocols, the induction regimen consisted of vincristine, doxorubicin, and dexamethasone (VAD) followed by first autologous stem cell transplantation (ASCT) prepared by melphalan 200 mg/m². Patients with an HLA-identical sibling donor were subsequently treated with dose-reduced allogeneic stem cell transplantation (IFM99-03 trial), and patients without an HLA-identical sibling donor were randomly assigned to undergo second ASCT prepared by melphalan 220 mg/m² and 160 mg dexamethasone with or without anti–IL-6 monoclonal antibody (IFM99-04 protocol). Two hundred eighty-four patients—65 in the IFM99-03 trial and 219 in the IFM99-04 trial—were prospectively treated and received at least one course of VAD. On an intent-to-treat basis, overall survival (OS) and event-free survival (EFS) did not differ significantly in the studies (medians 35 and 25 months in the IFM99-03 trial vs 41 and 30 months in the IFM99-04 trial, respectively). With a median follow-up time of 24 months, the EFS of the 166 patients randomly assigned in the tandem ASCT protocol was similar to the EFS of the 46 patients who underwent the entire IFM99-03 program (median, 35 vs 31.7 months), with a trend for a better OS in patients treated with tandem ASCT (median, 47.2 vs 35 months; P = .07). In patients with high-risk de novo MM, the combination of ASCT followed by dose-reduced allogeneic transplantation was not superior to tandem dose–intensified, melphalan-based ASCT.