Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting

Autologous hematopoietic cell transplantation (HCT) followed by nonmyeloablative allogeneic HCT (Auto/AlloHCT) provides cytoreduction and graft-versus-myeloma effects. We report on long-term outcomes of 102 patients with multiple myeloma who received Auto/AlloHCT with a median follow-up of 6.3 years. Treatment consisted of high-dose melphalan and autograft followed by 2 Gy total body irradiation, ± fludarabine and AlloHCT from HLA-identical siblings. Postgrafting immunosuppression was cyclosporine or tacrolimus and mycophenolate mofetil. Forty-two percent of patients developed grade 2-4 acute graft-versus-host-disease (GVHD) and 74% extensive chronic GVHD. Five-year non-relapse mortality after allografting was 18%, 95% related to GVHD or infections. Among 95 patients with detectable disease, 59 achieved complete remissions. Median time to progression was 5 years. Median overall survival (OS) was not reached. Median progression-free survival (PFS) was 3 years. Five-year OS and PFS were 64% and 36%, respectively. Seventy-three patients receiving AutoHCT within 10 months from treatment initiation had 5-year OS of 69% and PFS of 37%. In multivariate analysis, beta-2-microglobulin >3.5 µg/mL at diagnosis and Auto/AlloHCT >10 months after treatment initiation correlated with shorter OS (p=0.03 and p=0.02) and PFS (p=0.04 and p=0.03), while Karnofsky scores <90% at allotransplant correlated with shorter PFS only (p=0.005). Long-term disease control and GVHD remain key issues.