Bortezomib plus dexamethasone can improve stem cell collection and overcome the need for additional chemotherapy before autologous transplant in patients with myeloma.
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.
Corso
Alessandro
A
Division of Hematology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. a.corso@smatteo.pv.it
Barbarano
Luciana
L
Mangiacavalli
Silvia
S
Spriano
Mauro
M
Alessandrino
Emilio P
EP
Cafro
Anna Maria
AM
Pascutto
Cristiana
C
Varettoni
Marzia
M
Bernasconi
Paolo
P
Grillo
Giovanni
G
Carella
Angelo M
AM
Montalbetti
Luigi
L
Lazzarino
Mario
M
Morra
Enrica
E
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
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D005047:Etoposide; D003907:Dexamethasone; D003520:Cyclophosphamide; D002945:Cisplatin