Nonmyeloablative Unrelated Donor (URD) Hematopoietic Cell Transplantation (HCT) for the Treatment of Patients (pts) with Poor-Risk, Relapsed or Refractory Multiple Myeloma.

Abstract

We carried out HLA-matched URD peripheral blood stem cell (PBSC) transplant in 24 pts with poor-risk multiple myeloma after nonmyeloablative conditioning with fludarabine (90 mg/m2) and 2 Gy total body irradiation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. The median age of the 19 men and 5 women was 53 (23 – 66) years. Conventional metaphase cytogenetics obtained in 14 pts showed Δ13 in 6 pts and complex abnormalities in 9 pts. Stage III disease was present in 83% and 17% had stage II disease. The median time from diagnosis to URD HCT was 25 (range, 8–130) months, and 96% were beyond 1st complete remission (CR) or had never achieved CR1, despite multiple lines of chemotherapy (median 4.5, range 2–10). At study entry, 17 pts (71%) had chemotherapy-refractory disease and 14 pts (58%) had failed autologous HCT. Thirteen pts had planned autologous-URD tandem HCT, while 11 proceeded directly to URD HCT. The median follow-up was 2.5 years after allografting. One pt experienced non-fatal graft rejection. The incidences of acute grades II, III and chronic graft-versus-host disease were 54%, 13% and 75%, respectively. Non-relapse mortality was 22% at 2.5 years. CRs were observed in 11 pts (46%) and partial remissions (PR) in 3 (13%). Best disease responses were seen in pts given tandem autologous-URD HCT with CR in 8 pts and PR in 2 pts (77% CR+PR rate). The estimated overall survival (OS) at 2.5 years for all 24 pts was 65% and progression-free survival (PFS) 41%. Pts receiving tandem autologous-URD HCT had superior OS and PFS, 76% and 63% (Fig. A), compared to pts proceeding directly to URD HCT, 52% and 14% (Fig. B), respectively (PFS p-value=.03). Risk factors for worse OS included pts with significant medical comorbidities (p=.03), chemotherapy-refractory disease prior to HCT (p=.03), and pts who had failed autologous HCT (p=.07). Pts who failed autologous HCT had 48% OS and 30% PFS at 2.5 years. For pts with poor-risk, relapsed or refractory multiple myeloma, cytoreductive autologous HCT followed with nonmyeloablative conditioning and URD HCT is very promising treatment with low non-relapse mortality, high complete remission rates and prolonged PFS. The results also suggest that URD HCT may provide improved graft-versus-myeloma effect compared with HLA-matched sibling HCT without an increase in the risk of non-relapse mortality. [Display omitted]