A prospective, international phase 2 study of bortezomib retreatment in patients with relapsed multiple myeloma

• Published in: British journal of haematology 2013-03, Vol.160 (5), p.649-659
• Main Authors: Petrucci, Maria T., Giraldo, Pilar, Corradini, Paolo, Teixeira, Adriana, Dimopoulos, Meletios A., Blau, Igor W., Drach, Johannes, Angermund, Ralf, Allietta, Nathalie, Broer, Esther, Mitchell, Vivien, Bladé, Joan
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Boronic Acids - administration & dosage; Boronic Acids - adverse effects; Boronic Acids - therapeutic use; Bortezomib; Combined Modality Therapy; Dexamethasone - administration & dosage; Disease-Free Survival; Drug Resistance, Neoplasm; Europe; Female; Gastrointestinal Diseases - chemically induced; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - surgery; Neuropathy; Peripheral Nervous System Diseases - chemically induced; phase 2; Prospective Studies; Protease Inhibitors - administration & dosage; Protease Inhibitors - adverse effects; Protease Inhibitors - therapeutic use; Pyrazines - administration & dosage; Pyrazines - adverse effects; Pyrazines - therapeutic use; Recurrence; relapsed; retreatment; Salvage Therapy; Thalidomide - therapeutic use; Thrombocytopenia; Thrombocytopenia - chemically induced; Toxicity; Treatment Outcome; Tumors
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.12198

Summary Multiple myeloma (MM) typically follows a relapsing course with many patients requiring multiple therapies. This single‐arm phase 2 study prospectively evaluated the efficacy and safety of bortezomib retreatment in MM patients who had relapsed after achieving at least a partial response (≥PR) to prior bortezomib‐based therapy. Patients aged ≥18 years, with measurable, secretory MM, who relapsed ≥6 months after prior bortezomib treatment were eligible. Patients received up to eight cycles of bortezomib (±dexamethasone). The primary endpoint was best confirmed response at retreatment; secondary endpoints included duration of response (DOR), time to progression (TTP), and safety. Adverse events (AEs) were graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. A total of 130 patients (median of two prior lines of therapy) were enrolled and received retreatment. At retreatment, 28% and 72% of patients received bortezomib and bortezomib‐dexamethasone, respectively. Overall response rate was 40%. In patients who achieved ≥PR, median DOR and TTP were 6·5 and 8·4 months, respectively. Thrombocytopenia was the most common grade ≥3 AE (35%). Forty percent of patients experienced neuropathy events, which improved and resolved in a median of 1·5 and 8·9 months, respectively. In conclusion, bortezomib retreatment was effective and tolerable in relapsed MM patients, with no evidence of cumulative toxicities.