title: Phase II clinical trial for the evaluation of bortezomib within the reduced intensity conditioning regimen (RIC) and post-allogeneic transplantation for high-risk myeloma patients.
abstract: The current study was designed to assess the safety and efficacy of bortezomib in combination with fludarabine and melphalan as reduced intensity conditioning before allogeneic stem cell transplantation in patients with high risk multiple myeloma. Sixteen patients were evaluable. The median number of previous line of treatment was 3; all patients had relapsed following a prior autograft and 13 had previously received bortezomib. Fifteen of them either remained stable or improved disease status at day +100 post-transplant, including 11 patients with active disease. More specifically, nine patients (56%) and five patients (31%) reached complete remission and partial response, respectively. 25% developed grade III acute graft-versus-host disease. The cumulative incidence of non-relapse mortality, relapse and overall survival were 25%, 54% and 41%, respectively, at 3 years. Regarding the non-haematological toxicity (grade>2), two patients developed peripheral neuropathy, two patients liver toxicity and 1 pulmonary toxicity early post-transplant. The haematological toxicity was only observed during the first three cycles mostly related to low haemoglobin and platelet levels. The current trial is the first one evaluating the safety and efficacy of bortezomib as part of a reduced intensity conditioning regimen among patients with high risk multiple myeloma.
authors.affiliation: Servicio de Hematología, Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Caballero-Velázquez
authors.forename: Lucia
authors.initials: L
authors.lastname: López-Corral
authors.forename: Cristina
authors.initials: C
authors.lastname: Encinas
authors.forename: Cristina
authors.initials: C
authors.lastname: Castilla-Llorente
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martino
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.forename: Antonia
authors.initials: A
authors.lastname: Sampol
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
authors.forename: David
authors.initials: D
authors.lastname: Serrano
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Heras
authors.forename: Jesús
authors.initials: J
authors.lastname: San Miguel
authors.forename: José A
authors.initials: JA
authors.lastname: Pérez-Simón
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000627:therapeutic use; D004357:Drug Synergism; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D060046:Maintenance Chemotherapy; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000601:surgery*; D036102:Peripheral Blood Stem Cell Transplantation; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012074:Remission Induction; D012086:Reoperation; D016879:Salvage Therapy; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D001897:Boronic Acids; D007166:Immunosuppressive Agents; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D016572:Cyclosporine; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan
keywords: bortezomib; conditioning regimen; graft-versus-host disease; multiple myeloma; transplantation