The Association of a Salvage Treatment Containing Novel Agents Followed by Allogeneic Stem Cell Transplantation with Reduced-Intensity Conditioning Regimen Improves Overall Survival and Time-to-Progression in Multiple Myeloma Patiens Relapsing After Autologous Stem Cell Transplantation: A Multicentric Retrospective Study Based On Donor Availability.

Salvage treatments containing thalidomide, lenalidomide or bortezomib can induce a response rate in 30 to 60% of multiple myeloma (MM) patients (pts) relapsing after single or tandem autologous transplantation (auto-SCT) with a median response duration between 6 and 12 months. However, long-term disease control or cure cannot be commonly achieved. Allogeneic stem cell transplantation (allo-SCT) employing reduced intensity conditioning (RIC) has been increasingly performed in MM, but its efficacy in this clinical setting is still a matter of debate.

We investigated the role of RIC allo-SCT in MM pts who relapsed after auto-SCT and were then treated with a salvage therapy based on novel agents. In order to limit any selection bias, our study was structured similarly to an intention to treat analysis and included only those pts undergoing a HLA-typing immediately after the failure of auto-SCT. The cohort of pts having a donor (donor-group) was compared with the one not having a suitable donor (no-donor group).

One hundred thirty–six consecutive pts were retrospectively evaluated in a multicenter study. Fifty-seven found a donor and 50 (88%) underwent an allo-SCT: 16 identical sibling (32%), 34 MUD (68%). Conditioning regimens were fludarabine, melphalan±thiotepa in 21 patients (42%), fludarabine + 2 Gy TBI in 15 cases (30%), fludarabine and cyclophosphamide in 8 patients (16%) and fludarabine and treosulfan in the remaining 6 cases (12%). Seven pts having a donor did not receive allo-SCT for progressive disease or severe comorbidities. Median age of donor-group was significantly younger than no-donor group (53 versus 60 years, p=0,000045). No differences were detected between the donor and no-donor group with regard of median time between auto-SCT and relapse (17 months in both groups), treatment of first relapse (thalidomide-based 55% vs 31%, bortezomib-based 35% vs 46%, lenalidomide 10% vs 23%), median duration of salvage treatment (4,5 months versus 4 months) and percentage of responsive patients after treatment of first relapse (CR + VGPR 37% versus 30%, PR 46% vs 34%, SD 12% vs 18%, PD 5% vs 18%).

The median follow-up for all patients was 15 months (1-97) after relapse. The median time to progression (TTP) and overall survival (OS) for all patients were 16 and 25 months, respectively. Two-year TTP was 55% in the donor-group and 18% in the no-donor group (p<0.00001). Two-year OS was 57% in the donor-group and 48% in the no-donor group (p=0.004). In univariate analysis the availability of a donor and a duration of salvage treatment longer than 6 months significantly prolonged TTP (p=0.002 and p=0.008, respectively), while the availability of a donor and time from auto-SCT to relapse longer than 12 months significantly prolonged OS (P=0.009 and p=0.007, respectively). The 50 patients that actually proceeded to allo-SCT had a 1-year TRM of 8% and a 2-year TTP and OS of 53 % and 57%, respectively. Acute GVHD grade II-IV occurred in 19 patients (38%) and chronic GVHD in 14 patients (28%). In univariate analysis TTP was significantly prolonged for patients who were transplanted from sibling donors and for those who relapsed after at least 12 months after auto-SCT (p= 0.01 and p=0.05 respectively).

We conclude that the association of a salvage treatment containing novel agents consolidated by RIC allo-SCT seems a feasible strategy with a rather low mortality and an encouraging TTP and OS in patients relapsing after auto-SCT. Both availability of a donor as well as late (>12 months) relapse from auto-SCT positively impacted on OS.

Einsele:celgene: Research Funding; orthobiotech: Research Funding.