Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation (RIC allo-SCT) for Patients with High-Risk Multiple Myeloma (MM): A Survey from the Societe Francaise De Greffe De Moelle Et De Therapie Cellulaire.

The results of RIC allo-SCT for MM are still under considerable debate. While EBMT data did not support the universal use of RIC for MM allografts, the Italian and spanish randomized multicenter trials suggested that in newly diagnosed myeloma, outcome in recipients of a hematopoietic stem-cell autograft followed by RIC allo-SCT from an HLA-identical sibling is superior to that in recipients of tandem stem-cell autografts. The aim of this multicenter retrospective national study was to identify prognostic factors for outcome of high-risk patients with MM after allo-SCT prepared by RIC. Data from 219 patients (median age 52 years, range 27–66), who received grafts from a sibling (n=197) or unrelated donor (n=22) were analyzed. At time of transplant, only 37 patients (17%) received RIC allo-SCT in CR or VGPR, while 134 patients (61%) were transplanted in PR. 48 patients were transplanted either in stable disease (n=15) or were in refractory/ progressive disease (n=33). All patients have received at least one autologous transplant prior to RIC allo-SCT. The graft source was PBSCs in the majority of patients (n=183). 21% of the patients received the Seattle Fludarabine and low dose TBI RIC regimen, while 53% of patients received Fludarabine, Busulfan and ATG. 32 patients (15%) died of transplant-related complications. The incidences of grade 2–4 acute GVHD and extensive chronic GVHD were 37% and 20% respectively. At 3 years, overall and progression free survivals (OS, PFS) were 41% (95%CI, 34–49) and 19% (95%CI, 14–27) respectively. Disease status (CR, PR, SD vs. progressive) was significantly associated with overall survival (P=0.0002). In multivariate analysis, disease status at time of RIC allo-SCT, was the strongest parameter associated with an improved OS and PFS (P=0.005 and P=0.004 respectively). Despite its obvious caveats, the relatively low TRM observed in this series, suggest that there is still space to investigate RIC allo-SCT for MM. However, RIC allo- SCT appears to result in a durable response only if it is applied early in the disease history, especially when patients are still chemosensitive. Since the latter results are also expected to be further improved with the systematic and early use of maintenance therapies (Bortezomib and/or Lenalidomide) after RIC allo-SCT, randomized or quasirandomized prospective studies are still warranted.