170: Long-Term Outcome of Nonmyeloalative Allografting from HLA-Identical Sibling for Multiple Myeloma (MM)

Background: Allogeneic hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning may be used with lower transplant-related mortality (TRM) in elderly patients (pts) and/or those with comorbidities. In this approach anti-tumor activity relies on graft-versus-tumor effects. Here we analyzed outcomes of nonmyeloablative allografts from HLA-identical sibling performed by a multicenter consortium in pts with multiple myeloma (MM) with a median follow up (FU) of 5 years(y). Patients: Between March 1998 and February 2007, 133 pts with stage II-III MM received alloHCT following 2 Gy TBI +/- fludarabine (48/133 pts). Median age was 52 (range 31–71) y. Forty-eight and 7 pts (36% and 5%) were older than 55 and 65 y, respectively, and 43% had HCT specific comorbidity scores >1. Median number of prior treatments was 1(range 1–6) and 44 pts (33%) received 2 or more lines of therapy. One hundred two pts (77%) received their allografts as consolidation following cytoreductive autografts (conditioning in 97% of pts: melphalan 200 mg/m2). Postgrafting immunosuppression was mycophenolate mofetil (MMF) and cyclosporine (n = 116, 87%) or tacrolimus (n = 17, 13%). At allografting 86 pts (65%) had chemoresponsive disease with 33 and 53 pts (25% and 40%) in complete (CR) and partial remission (PR), respectively, while 32 and 15 pts (24% and 11%) had chemorefractory and progressive disease respectively. Results: Median FU for surviving pts was 5(range 0.3–8.5)y. Fifty four(41%) and 12 pts (9%) had grade 2 to 4 and 3 to 4 acute graft-versus-host-disease (GVHD); 86 pts (65%) had extensive chronic GVHD. The overall response rate was 89%, with 73(55%) and 46(34%) pts achieving CR and PR, respectively. Median time to progression was 3.6 y. Median progression-free survival (PFS) was 2.7 y, and 5-y estimated PFS was 28%. Nonrelapse mortalities (NRM) at 100 days, 1 and 5 y were 1%, 13% and 24%. Median overall survival (OS) was reached after 6.2 y, and 5-y estimated OS was 54%. In the subset of 102 pts who received a tandem auto/allografts, the median time to progression was 4 y, median PFS was 3 y while median OS has not been reached. In this group estimated PFS and OS at 3 and 5-years were 69% and 40%, 80% and 55% respectively. Conclusion: Nonmyeloablative allografting, in particular as part of a planned tandem auto/allo HCT protocol, is a treatment option for MM pts with HLA identical siblings. Future studies are aimed at improving long-term disease control and reducing GVHD.