Long-Term Follow-up Results of IFM9903 and IFM9904 Trials Comparing Non Myeloablative Allotransplantation with Autologous Transplantation in High-Risk De Novo Multiple Myeloma

The IFM99-03 and IFM99-04 trials were conducted from April 2000 to August 2004. Patients younger than 66 years with high-risk (b2microglobulin > 3 and chromosome 13 deletion by FISH analysis at diagnosis) de novo multiple myeloma (MM) were included and prospectively treated. In both protocols, induction regimen consisted of VAD (4 courses) followed by melphalan 200 mg/m2 (HDM200) plus autologous peripheral blood stem cell transplantation (ASCT). When a HLA-sibling donor was available, ASCT was followed by reduced-intensity conditioning regimen (RIC) allograft (fludarabine, antithymocyte globulin and low dose busulfan): IFM9903 protocol (Garban et al, Blood 2006;107:3474-3480). When no donor was available, patients were randomised to receive a second ASCT with HDM220 +/- anti-IL6 monoclonal antibody (BE-8, 250 mg total dose, Diaclone Besançon, France): IFM99-04 protocol (Moreau et al, Blood 2006;107:397-403).284 patients met eligibility criteria and received at least one course of VAD. 65 had an available HLA-identical sibling donor and were included in the IFM99-03 trial, and 219 were included in the IFM 99-04 trial. Patients were older in the tandem ASCT trial (median age, 58 vs 54 years; P  = .006) and the b2-microglobulin level was also higher in the latter group (median, 4.9 mg/L vs 4.1 mg/L; P = .049).
At the reference date of July 1^st, 2008, on an intent-to-treat basis, considering the entire population of 284 patients, with a median follow-up of 56 months, the EFS did not significantly differ from tandem ASCT to single autograft followed by allo-RIC (median 22 vs 19 months, P = 0.58). Nevertheless, there was a trend for a superior OS in the double ASCT trial (median 48 vs 34 months, P = 0.07). When considering the comparison of the results of the 166 patients / 219 who completed the whole tandem ASCT protocol with those of the 46 patients / 65 who underwent the entire auto/allo-RIC program, no difference was observed regarding EFS (median 25 vs 21 months, P = 0.88), but there was again a trend for a superior OS in favour of double ASCT (median OS, 57 vs 41 months, P = 0.08), due to a longer survival after relapse in the tandem ASCT arm.
These long-term results indicate that, in a subgroup of high-risk patients with de novo MM, a tandem autologous transplant procedure is at least equivalent or even superior to a combination of autologous followed by RIC allogeneic stem cell transplantation.