title: 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.
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/m(2) 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.
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Alekshun
authors.forename: Kenneth
authors.initials: K
authors.lastname: Shain
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sullivan
authors.forename: Rachid
authors.initials: R
authors.lastname: Baz
authors.forename: Lia
authors.initials: L
authors.lastname: Perez
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Kharfan-Dabaja
authors.forename: Jose L
authors.initials: JL
authors.lastname: Ochoa-Bayona
authors.forename: Hugo F
authors.initials: HF
authors.lastname: Fernandez
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Yarde
authors.forename: Vasco
authors.initials: V
authors.lastname: Oliveira
authors.forename: William
authors.initials: W
authors.lastname: Fulp
authors.forename: Gang
authors.initials: G
authors.lastname: Han
authors.forename: Jongphil
authors.initials: J
authors.lastname: Kim
authors.forename: Dung-Tsa
authors.initials: DT
authors.lastname: Chen
authors.forename: Jyoti
authors.initials: J
authors.lastname: Raychaudhuri
authors.forename: William
authors.initials: W
authors.lastname: Dalton
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D018450:Disease Progression; D051856:Fanconi Anemia Complementation Group Proteins / Q000378:metabolism; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D011719:Pyrazines / Q000008:administration & dosage; D016879:Salvage Therapy; D015398:Signal Transduction; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D051856:Fanconi Anemia Complementation Group Proteins; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan