Improved Survival for 149 First-Line Multiple Myeloma (MM) Patients (pts) Treated by Tandem Autologous (Auto)/Allogeneic (Allo) Stem Cell Transplantation (SCT) : Retrospective Study of the Société Française de Greffe de Moelle Thérapie Cellulaire (SFGM-TC).

Tandem autologous (auto)/allogeneic (allo) stem cell transplantation (SCT) is a promising approach in patients (pts) with multiple myeloma (MM), that combines cytoreduction and graft-versus-myeloma effect. Whether tandem auto/allo SCT should be proposed per se as part of up-front treatment or as salvage therapy, is still a matter of debate. Here we report on a retrospective analysis of 149 MM pts treated at 20 centers of the Société Française de Greffe de Moelle Thérapie Cellulaire (SFGM-TC).

149 pts with MM received tandem auto/allo SCT between November 1998 and June 2009. At diagnosis pts characteristics were as follows: Salmon-Durie stage III, 114 pts (76%) and stage II, 25 pts (17%); mean age 51 (range 21-67) years; M/F 88/61; Ig subtype, IgG 79 pts (53%), IgA 27 pts (18%) and light chains 32 pts (21%). Sixty six pts (44%) received tandem as part of up-front treatment and 83 (56%) as salvage therapy for first or subsequent relapse. For the entire cohort, median time between diagnosis and tandem auto/allo SCT was 7.4 months (range 2-339.7). Auto SCT conditioning was with HD Melphalan in 147 pts. Median time between auto and allo SCT was 3.2 months (range 1.1-12.4). 116 pts (77%) received allo SCT from siblings and 33 pts (22%) from unrelated donors. One allo SCT was haplo-identical. Mean donor age was 49 years (range 22-68). Stem cell source was PBSC in 139 pts (93%), BM 6 pts (4%) and cord blood in 4 pts (3%). Allogeneic SCT conditioning was myeloablative in 20 pts (13%) and included Cyclophosphamide in 70% of cases, whereas it was non myeloablative in 129 pts (87%) and included Busulfan and Fludarabine in 61% of cases. Post allografting immunosuppression was with Cyclosporine (n=134; 90%) and/or Mycophenolate Mofetil (n=39; 26%). The disease status at allo SCT included complete remission (CR, 25 pts, 17%), very good partial remission (VGPR, 14 pts, 9%), partial remission (PR, 85 pts, 57%), refractory disease (RD, 15 pts, 10%) and progressive disease or relapse (PD/relapse, 10 pts, 7%).

All pts except 3 had sustained donor engraftment. The overall response rate was 69%, with 52 (35%), 20 (13%) and 31 pts (21%) achieving CR, VGPR and PR respectively. Median follow-up from allo SCT was 36.5 months (range 1-119). Overall survival (OS) was 51.4% (42-61) at 3 years. Cumulative incidence of transplant related mortality (TRM) at 100 days was 10% and was mostly related to infection. A single line of treatment before tandem auto/allo SCT was associated with improved OS: 3-year-OS was 55% (95% confidence interval: 42-67) for pts in first line at tandem auto/allo SCT and 35% (95% CI: 21-50) for pts treated by >1 line (p=0.03). Thirty nine (26%) experienced grade I to II acute graft-versus-host-disease (GVHD) and 20 pts (13%) grade III to IV. Seventeen (11%) had limited and 27 pts (18%) extensive chronic GVHD. OS was 57% (46-67) for pts with grade I to II acute GVHD and 21% (2-40) for pts with grade III to IV acute GVHD (p<0.0001). However, extensive chronic GVHD had no statistically significant impact on OS.

Our results suggest that the number of treatment lines received before tandem auto/allo SCT is an important issue, with an improved OS for pts treated by a single line before tandem. Moreover, better control of acute GVHD might further improve survival. These findings might be confirmed by phase III clinical trials.

No relevant conflicts of interest to declare.