Efficacy and safety of once-weekly bortezomib in multiple myeloma patients

• Published in: Blood Vol. 116; no. 23; pp. 4745 - 4753
• Main Authors: Bringhen, Sara, Larocca, Alessandra, Rossi, Davide, Cavalli, Maide, Genuardi, Mariella, Ria, Roberto, Gentili, Silvia, Patriarca, Francesca, Nozzoli, Chiara, Levi, Anna, Guglielmelli, Tommasina, Benevolo, Giulia, Callea, Vincenzo, Rizzo, Vincenzo, Cangialosi, Clotilde, Musto, Pellegrino, De Rosa, Luca, Liberati, Anna Marina, Grasso, Mariella, Falcone, Antonietta P., Evangelista, Andrea, Cavo, Michele, Gaidano, Gianluca, Boccadoro, Mario, Palumbo, Antonio
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 02.12.2010; Americain Society of Hematology
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Boronic Acids - administration & dosage; Boronic Acids - adverse effects; Bortezomib; Disease-Free Survival; Drug Administration Schedule; Female; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Incidence; Kaplan-Meier Estimate; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Melphalan - administration & dosage; Melphalan - adverse effects; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Multiple Myeloma - pathology; Neoplasm Staging; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - epidemiology; Prednisone - administration & dosage; Prednisone - adverse effects; Pyrazines - administration & dosage; Pyrazines - adverse effects; Thalidomide - administration & dosage; Thalidomide - adverse effects; Treatment Outcome; Antineoplastic agent; Human; Immunopathology; Bortezomib; Hematology; Treatment efficiency; Malignant hemopathy; Myeloma; Immunoglobulinopathy; Analog; Proteasome inhibitor; Lymphoproliferative syndrome; Dipeptides; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2010-07-294983

In a recent phase 3 trial, bortezomib-melphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic toxicities, the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions: 372 patients received once-weekly and 139 twice-weekly bortezomib. In this post-hoc analysis we assessed the impact of the schedule change on clinical outcomes and safety. Long-term outcomes appeared similar: 3-year progression-free survival rate was 50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year overall survival rate was 88% and 89%, respectively (P = .54). The complete response rate was 30% in the once-weekly and 35% in the twice-weekly group (P = .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly patients and 51% of twice-weekly patients (P = .003). The incidence of grade 3/4 peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group discontinued therapy because of peripheral neuropathy (P < .001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179.