1. 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.
- Author
-
Nishihori, Taiga, Alekshun, Todd J., Shain, Kenneth, Sullivan, Daniel M., Baz, Rachid, Perez, Lia, Pidala, Joseph, Kharfan-Dabaja, Mohamed A., Ochoa-Bayona, Jose L., Fernandez, Hugo F., Yarde, Danielle N., Oliveira, Vasco, Fulp, William, Han, Gang, Kim, Jongphil, Chen, Dung-Tsa, Raychaudhuri, Jyoti, Dalton, William, Anasetti, Claudio, and Alsina, Melissa
- Subjects
KARYOTYPES ,CHROMOSOME abnormalities ,STATISTICAL hypothesis testing ,MULTIPLE myeloma ,MESSENGER RNA ,STEM cells - Abstract
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/m
2 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. [ABSTRACT FROM AUTHOR]- Published
- 2012
- Full Text
- View/download PDF