Tandem Auto/AlloHCT for Newly Diagnosed Multiple Myeloma (MM) Patients

BACKGROUND: Non-myeloablative allotransplantation following autologous HCT (Tandem Auto/AlloHCT) provides cytoreduction and graft-versus-myeloma effects. Tandem Auto/AlloHCT has been compared with double autologous HCT by three groups (Garban, et al. 2006; Bruno et al. 2007; Rosiñol et al. 2008) and a large prospective study, the BMT-CTN 0102 trial, is ongoing. We previously reported results in 102 patients (pts) with HLA-identical siblings treated by Seattle Consortium Centers (ASH 2007, abstract #3029). Here we report on pts who fulfilled the entry criteria for the BMT-CTN 0102 trial, having received Tandem Auto/AlloHCT within 10 months from initial therapy.

PATIENTS: Pts with stage II-III MM (n=73) received Tandem Auto/AlloHCT at 8 centers between December 1998 and August 2005. Median age was 51 (range 35–66) years. Median number of prior treatments was 1 (1–2), and median number of prior treatment cycles was 4 (2–12). Median time between initiation of treatment and autografting was 7 (3.4–10) months. Median time between auto and allo HCT was 67 (40–281) days. Autologous HCT conditioning was with melphalan 200 mg/m² and allogeneic conditioning with 2 Gy total body irradiation (TBI) alone (n=56; 77%) or 2 Gy TBI plus fludarabine 90 mg/m2 (n=17; 23%). Post allografting immunosuppression was with mycophenolate mofetil (MMF) and cyclosporine (n=67; 92%) or MMF and tacrolimus (n=11; 8%). The disease status at allogeneic HCT included complete remission (CR, 15 pts, 21%), very good partial remission (VGPR, 16 pts, 22%), partial remission (PR, 30 pts, 41%), refractory disease (RD, 10 pts, 14%) and progressive disease (PD, 2 pts, 2%).

RESULTS: All pts had sustained donor engraftment. Thirty one (41%) and 4 pts (5%), respectively, experienced grade 2 to 4 and 3 to 4 acute graft-versus-host-disease (GVHD); 54 pts (74%) had extensive chronic GVHD. The overall response rate was 94%, with 50 (68%), 5 (7%) and 14 pts (19%) achieving CR, VGPR and PR respectively. After a median follow-up of 6.4 (2–9) years from allografting, median time to progression was 4.6 years. Median overall survival (OS) has not been reached. Median progression-free survival (PFS) was 3.9 years. Five-year estimated OS and PFS were 69% and 37% respectively. Cumulative incidence of nonrelapse mortality (NRM) at 100 days, 1 and 5 years were 1%, 10% and 16% respectively. Most (83%) of the NRM was related to GVHD and/or infection. Considering the whole group of patients given tandem Auto/Allo (n=102), serum beta-2 microglobulin level ³3.5 ug/ml at diagnosis and Karnofsky score <90% at allo HCT were associated with higher risk of relapse (p=0.008 and p=0.01) and relapse plus NRM (p=0.04, and p=0.005) by multivariate analysis.

CONCLUSION: Long-term disease control and GVHD and its complications remain key issues to address. Confirmation of these outcomes and comparison with tandem autologous HCT await results of the BMT-CTN 0102 trial.