Salvage non-myeloablative allogeneic transplantation after failure of an autologous transplantation in multiple myeloma

Introduction: Salvage therapy for patients relapsing after an autologous stem cell transplant for multiple myeloma is not well defined. Allogeneic stem cell transplantation with a reduced-intensity preparative regimen has been one of the approaches used in this setting. We analyzed the outcomes of 30 patients who underwent a reduced-intensity allogeneic transplant after disease progression from the first autologous transplant. Methods: Median age was 51 years (range 32–65). Twenty-two patients underwent transplants from a related donor (21 HLA-identical, 1 with a single class 1 antigen mismatch), while 8 from an unrelated donor (7 HLA-identical, one with a single DQ mismatch). Preparative regimen in 28/30 patients was a combination of fludarabine 30 mg/m2 × 4 days and melphalan 70 mg/m2 IV × 2 days (24 patients), while 2 patients received fludarabine 25 mg/m2 IV × 5d and cyclophosphamide 1g/m2 IV × 3d. Patients undergoing unrelated donor transplants also received the rabbit ATG. Tacrolimus and methotrexate were used for GVHD prophylaxis. The median interval between the first and the second transplant was 18 months. Seventeen patients had resistant and progressive disease. These patients had received a median of 5 chemotherapy regimens prior to transplant. In 21/30 patients with available cytogenetic studies, 14 were normal and 7 abnormal. Results: Twenty-one of the 30 patients (70%) achieved a complete (8) or partial response (13). With a median follow up of 19 months (4–75), 1-year progression-free survival (PFS) was 24% and 1-year overall survival (OS) was 59%. Median PFS and OS were 7 and 16 months, respectively. One-year non-relapse mortality was 17%. Acute grade II/IV GVHD was seen in 9/30 (30%) and chronic GVHD in 13/30 (43%: limited 16%, extensive 27%) patients. Disease progression remained the major cause of failure with 14 (46%) dying of progressive disease. On univariate analysis, an interval of <1 year between two transplants was a predictor of early progression (P = .02) and the presence of progressive/ resistant disease showed a trend towards shorter overall survival (P = .07). Conclusions: Salvage allogeneic transplantation can achieve responses in 70% of heavily pretreated patients, with acceptable toxicity and durable remissions in patients treated more than a year after a prior autograft. Patients with chemosensitive disease seem to have a longer overall survival.