Bortezomib salvage followed by a Phase I/II study of bortezomib plus high-dose melphalan and tandem autologous transplantation for patients with primary resistant myeloma

Summary We conducted a Phase 1/2 study of bortezomib administered in combination with high‐dose melphalan followed by tandem autologous transplants in patients with primary resistant multiple myeloma. Thirty patients received two cycles of salvage bortezomib followed by stem cell mobilization with granulocyte colony‐stimulating factor and harvest. Melphalan 100 mg/m2 per day on two consecutive days was administered, immediately followed by one dose of bortezomib (dose escalation) and stem cell infusion. The median beta 2‐microglobulin was 4·35 mg/l (range: 1·8–11·4); albumin was 37 g/l (range: 3·1–4·9); high‐risk karyotypes were noted in 45% of patients. The maximum planned dose of bortezomib at 1·3 mg/m2 was well tolerated and a formal maximum tolerated dose was not determined. The peak of best overall response (≥partial response) and complete response rates after tandem transplants were 84% and 36%, respectively. With a median follow‐up of 48 months, the median progression‐free survival was 15 [95% confidence interval (CI): 11–21] months and the median overall survival was 35 (95% CI: 22–43) months. Correlative studies demonstrated decreased expression of BRCA2 (P = 0·0072) and FANCF (P = 0·0458) mRNA following bortezomib treatment. Bortezomib combined with high‐dose melphalan is a well‐tolerated conditioning with some activity in patients with resistant myeloma.