Non-Myeloablative Allogeneic Transplantation in Patients with Relapsed or Refractory Multiple Myeloma.

Patients with recurrent and refractory multiple myeloma have a very limited survival expectance. Allogeneic transplantation might offer an option for cure in myeloma and the recent development of non-myeloablative conditioning regimens has reduced transplant related morbidity and mortality and rendered this treatment feasible in elderly patients.

The role of non-myeloablative allogeneic transplantation for multiple myeloma however, has not yet been defined. We have analyzed the results of patients with relapsed or refractory multiple myeloma treated at our institution.

Between 08/1999 and 02/2004, 56 patients with relapsed (n=54) or refractory (n=2) myeloma were treated with non-myeloablative allogeneic transplantation. The median beta2microglobulin at the time of diagnosis was 2.75 mg/l, and median age at the time of transplant was 54.5 years (39.2–67.8). The median time from diagnosis to transplant was 3.6 years. Prior to allogeneic transplantation, patients received reinduction chemotherapy which included an autologous transplantation for 30 patients. The median number of previous cycles of conventional chemotherapy was 9. The conditioning regimen was 2 Gy TBI with (n=43) or without (n=3) fludarabin 3 x 30 mg/m² for 46 patients, the remaining 10 patients received a melphalan containing regimen.

Acute toxicity was low with a WBC < 500/μl and platelets < 50/μl for a median of 0 days. Engraftment was prompt with 90 % of patients having achieved > 90 % donor chimerism by day 56. Acute GvHD Grade II-IV occurred in 36 % of patients with 22 % Grade III-IV, and 61 % experienced chronic GvHD. Total transplant related mortality reached 20 %, with a day 100 TRM of 5 %. 32 patients experienced relapse or progressive disease, and 32 % of patients died due to relapse. The Kaplan-Meier estimate of overall survival and progression free survival at 18 months was 40 % and 25 %, respectively, with a median follow up of survivors of 21 months. Patients who experienced cGvHD had a significantly higher overall survival estimate (60 % vs. 20 % at 18 months, p=0.03). The number of cycles of pretreatment before allogeneic transplantation had a statistically significant negative influence on overall (p=0.02) and progression free survival (p=0.006).

We conclude that non-myeloablative allogeneic transplantation is feasible in patients with relapsed multiple myeloma. The significant poor prognostic factors we identified were absence of chronic GvHD and number of cycles of pretreatment. Allogeneic transplantion should therefore be considered as an option earlier in the course of the disease.