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KOS 2007: Long-Term and Updated Results of the IFM99-03 and IFM99-04 ProtocolsComparing Autologous Followed by RIC-Allogeneic Transplantation and Double Transplant in High-Risk De Novo Multiple Myeloma
Philippe Moreau, MD
on Behalf of the IFM Group

AUTHORS: P. Moreau, F. Garban, T. Facon, C. Hulin, M. Attal, L. Benboukher, G. Marit, J.G. Fuzibet, C. Doyen, S. Leyvraz, P. Casassus, M. Michallet, C. Mathiot, I. Yacoub-Agha, L. Garderet, J.L. Harousseau on behalf the IFM group
University Hospital of Nantes, Grenoble, Lille, Nancy, Toulouse, Tours, Bordeaux, Nice, Bruxelles, Lausanne, Paris, Lyon, France

The IFM99-03 and IFM99-04 trials were conducted from 04/2000 to08/2004. Pts younger than 66 years with high-risk (b2mic > 3 and chromosome13 deletion at diagnosis) de novo multiple myeloma (MM) wereprospectively treated according to HLA-identical sibling availability. Inboth protocols, induction regimen consisted of VAD followed by melphalan200 mg/m2 plus autologous SCT. When a HLA-sibling donor wasavailable, ASCT was followed by RIC-allogeneicSCT (fludarabine, ATGand low dose busulfan): IFM9903 protocol (Garban, Blood2006;107:3474). When no donor was available, pts were randomised toreceive a second ASCT with HDM220 ± anti-IL6 moAb: IFM99-04 protocol(Moreau, Blood 2006;107:397). 284 pts met eligibility criteria andreceived at least one course of VAD. 65 had an available HLA-identicalsibling donor and were included in the IFM99-03 trial, and 219 were included in the IFM 99-04 trial. At the reference date of November 1,2006, on an intent-to-treat basis, considering the entire population of 284pts, with a median follow-up of 38 months for living pts, EFS did not differsignificantly between studies (median EFS 22 months in the IFM99-04 trial vs 18 in the IFM99-03 protocol; p=0.14). Conversely, OS was significantlysuperior in the tandem ASCT trial (median OS 56 months inthe IFM99-04 trial vs 34 in the IFM99-03 protocol; p=0.03). OS and EFSwere similar in the 2 treatment arms of the IFM99-04 trial (second ASCTwith HDM220 + anti-IL6 moAb, n = 81, or second ASCT with HDM220without anti-IL6 moAb, n = 85); thus, the results of pts in both arms werepooled for comparison with those of 46 pts who underwent the entireASCT plus RIC-allogeneic transplantation program. EFS of the 166 ptsrandomly assigned in the tandem ASCT protocol was similar to the EFSof the 46 pts who underwent the entire IFM99-03 program (median, 25months vs 21; p=0.38). Conversely, OS was significantly superior forthe randomly assigned pts in the tandem ASCT trial than for patientstreated with the combination of ASCT followed by RIC-allogeneic transplantation(median OS, 59 months vs 35; p=0.016), due to a longer survivalafter relapse in the tandem ASCT arm. These long-term resultsindicate that, in a subgroup of high-risk pts with de novo MM, a tandemASCT procedure is superior to a combination of ASCT followed by RICallogeneicSCT. The better OS described in the tandem ASCT trial isrelated to a better feasibility of salvage regimens after relapse.

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