title: Bortezomib plus dexamethasone can improve stem cell collection and overcome the need for additional chemotherapy before autologous transplant in patients with myeloma.
abstract: The aim of this phase II trial was to investigate the efficacy of bortezomib plus dexamethasone (Vel-Dex) as induction therapy in patients with multiple myeloma (MM) and to define the role of intensification before transplantation. Fifty-seven patients were treated with four courses of Vel-Dex, two cycles of dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP), and a single autologous transplant. Fourteen patients (25%) went off-study: seven after Vel-Dex, seven after DCEP. All patients yielded high numbers of stem cells (median CD34+ cells 7.5 x 106/kg); 54 of the 57 patients (94%) collected > or =4 x 106/kg CD34+ cells, 60% with a single leukapheresis. The overall response rate (ORR) after Vel-Dex was 86% (70% had a very good partial response [VGPR] or better) regardless of cytogenetic abnormalities and International Staging System stage (ISS). The response at the end of the two DCEP cycles remained unchanged in 35 patients (70%), worsened in 15 (20%), and improved in 5 (10%). Because of the consistent drop-out, the ORR in intention-to-treat analysis decreased significantly from 86% after Vel-Dex to 76% after DCEP, and 73% after transplantation. However, when considering the subset of 43 patients who completed the program, the ORR was 96% (complete response 39%, VGPR 41%, partial response 16%). In conclusion, Vel-Dex produces high response rates, improves stem cell collection, and overcomes the need for intensification before autologous transplantation.
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. a.corso@smatteo.pv.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corso
authors.forename: Luciana
authors.initials: L
authors.lastname: Barbarano
authors.forename: Silvia
authors.initials: S
authors.lastname: Mangiacavalli
authors.forename: Mauro
authors.initials: M
authors.lastname: Spriano
authors.forename: Emilio P
authors.initials: EP
authors.lastname: Alessandrino
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Cafro
authors.forename: Cristiana
authors.initials: C
authors.lastname: Pascutto
authors.forename: Marzia
authors.initials: M
authors.lastname: Varettoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernasconi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grillo
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Carella
authors.forename: Luigi
authors.initials: L
authors.lastname: Montalbetti
authors.forename: Mario
authors.initials: M
authors.lastname: Lazzarino
authors.forename: Enrica
authors.initials: E
authors.lastname: Morra
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003248:Constipation / Q000139:chemically induced; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007239:Infections / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D005047:Etoposide; D003907:Dexamethasone; D003520:Cyclophosphamide; D002945:Cisplatin