Tandem autologous/allogeneic hematopoietic cell transplantation with bortezomib maintenance therapy for high-risk myeloma.

We evaluated tandem autologous/allogeneic hematopoietic cell transplantation followed by bortezomib maintenance therapy in a prospective phase 2 trial of treatment of high-risk multiple myeloma. The high-dose conditioning regimen for autologous hematopoietic cell transplantation consisted of melphalan 200 mg/m. The nonmyeloablative conditioning regimen for the allogeneic transplant involved low-dose total body irradiation (2 Gy) with or without fludarabine (30 mg/m × 3 days). Among the 31 patients enrolled, 26 (84%) proceeded to HLA-matched allogeneic hematopoietic cell transplantation at a median of 61 (range, 41-168) days following the autologous transplant. Twenty-one patients (68%) started bortezomib (1.6 mg/m IV or 2.6 mg/m subcutaneously every 14 days for 9 months) at a median of 79 (range, 63-103) days after allogeneic transplantation. With a median follow-up of 51 (range, 16-86) months and based on intention to treat, the 2-year and 4-year progression-free survival and overall survival estimates among 24 newly diagnosed high-risk patients were 71% and 75%, and 52% and 61%, respectively. The 7 patients enrolled with relapsed or persistent disease had a 2-year and 4-year progression-free survival and overall survival rates of 14% and 43%, and 14% and 29%, respectively. These findings suggest that for patients with newly diagnosed high-risk multiple myeloma, bortezomib maintenance therapy after tandem autologous/allogeneic hematopoietic cell transplantation is safe and may prevent disease progression until full establishment of a graft-versus-myeloma effect. This benefit, however, does not extend to patients who enroll after unsuccessful prior therapy. This trial was registered at www.clinicaltrials.gov as #NCT00793572.