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

• Published in: British journal of haematology 2013-08, Vol.162 (4), p.474-482
• Main Authors: Caballero‐Velázquez, Teresa, López‐Corral, Lucia, Encinas, Cristina, Castilla‐Llorente, Cristina, Martino, Rodrigo, Rosiñol, Laura, Sampol, Antonia, Caballero, Dolores, Serrano, David, Heras, Inmaculada, San Miguel, Jesús, Pérez‐Simón, José A.
• Format: Article
• Language: English
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis - drug effects; Biological and medical sciences; Boronic Acids - administration & dosage; Boronic Acids - adverse effects; Boronic Acids - pharmacology; Boronic Acids - therapeutic use; Bortezomib; Chemical and Drug Induced Liver Injury - etiology; Combined Modality Therapy; conditioning regimen; Cyclosporine - therapeutic use; Drug Synergism; Female; Graft vs Host Disease - epidemiology; graft‐versus‐host disease; Hematologic and hematopoietic diseases; Hematologic Diseases - chemically induced; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Maintenance Chemotherapy; Male; Medical sciences; Melphalan - administration & dosage; Melphalan - therapeutic use; Middle Aged; multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - surgery; Peripheral Blood Stem Cell Transplantation; Peripheral Nervous System Diseases - chemically induced; Protease Inhibitors - administration & dosage; Protease Inhibitors - adverse effects; Protease Inhibitors - pharmacology; Protease Inhibitors - therapeutic use; Pyrazines - administration & dosage; Pyrazines - adverse effects; Pyrazines - pharmacology; Pyrazines - therapeutic use; Remission Induction; Reoperation; Salvage Therapy; T-Lymphocyte Subsets - drug effects; transplantation; Transplantation Conditioning - methods; Transplantation, Autologous; Transplantation, Homologous; Tumors; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives; Vidarabine - therapeutic use
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.12410

Summary 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.