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).
Authors: Fabre Claire , Koscielny Serge , Harousseau Jean-Luc , Mohty Mohamad , Blaise Didier , Milpied Noël , Rio Bernard , Michallet Mauricette , Facon Thierry , Vernant Jean-Paul , Buzyn Agnès , Socié Gérard , Cahn Jean-Yves , Maillard Natacha , Bay Jacques-Olivier , Bourhis Jean-Henri 
Published: October 2019

Abstract
Abstract 1188
Poster Board I-210

BACKGROUND:
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).

PATIENTS:
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%).

RESULTS:
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.

CONCLUSION:
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.

Disclosures:
No relevant conflicts of interest to declare.