Nonmyeloablative Allogeneic HCT From Unrelated Donors for Multiple Myeloma (MM).

We previously reported on the outcome of unrelated donor nonmyeloablative hematopoietic cell transplantation (HCT) in 24 patients (pts) with poor-risk multiple myeloma treated by Seattle Consortium Centers (Georges et al BBMT 2007). Here we update our observation to 43 pts with a median follow up of 3.3 years after allografting.

Pts with stage II-III MM (n=43) received AlloHCT at 9 centers between May 2000 and September 2008. Forty pts (93%) were matched with their donors for 10 of 10 HLA alleles, and 3 (7%) had single HLA-C allele-level mismatches. Median age at allotransplant was 53 (range 35–67) years. Median number of prior treatments was 2 (1–3), and median number of prior treatment cycles was 8 (5–22). All pts but 2 received at least 1 (range 1-3) high dose-Autograft regimen. Fifteen pts (35%) received planned tandem Auto/AlloHCT as consolidation to first line therapy. Allogeneic conditioning was with 2 Gy TBI plus fludarabine 90 mg/m2 and post allografting immunosuppression was with mycophenolate mofetil (MMF) and cyclosporine or tacrolimus. Disease status at allogeneic HCT included complete remission (CR, 6 pts, 14%), very good partial remission (VGPR, 12 pts, 28%), partial remission (PR, 14 pts, 33%) and refractory disease (RD, 11 pts, 26%).

All pts had sustained donor engraftment. Twenty-eight (65%) developed grade 2 to 4 acute graft-versus-host-disease (GVHD) and 6 pts (14%) developed 3 to 4 acute GVHD. Twenty-six pts (60%) had extensive chronic GVHD. The overall response rate was 86%, with 18 pts (42%) achieving CR, 14 (33%) VGPR and 5 (12%) PR. With a median follow-up of 3.3 (0.3–8.1) years from allografting, median time to progression was 1.1 years. Median overall survival (OS) has not been reached. Median progression-free survival (PFS) was 1.5 years. Five-year estimated OS and PFS were 51% and 21% respectively. Cumulative incidence of nonrelapse mortality (NRM) at 100 days, 1 and 5 years were 2%, 16% and 19% respectively. The subgroup of 15 pts receiving upfront tandem Auto/AlloHCT had five-year estimated OS and PFS of 72% and 37%, respectively. These results are similar to the outcomes we observed in a series of 102 patients with MM who received upfront tandem Auto/AlloHCT from HLA-identical sibling donor (Rotta et al, Blood 2009) where five-year OS and PFS were 64% and 36%, respectively.

The use of unrelated donors leads to sustained donor engraftment and is associated with a low 1-year NRM (16%). As consolidation of first remission, Tandem Auto/Allo HCT leads to similar 5-year outcomes as HCT from HLA-identical sibling donors.

No relevant conflicts of interest to declare.