title: A prospective, international phase 2 study of bortezomib retreatment in patients with relapsed multiple myeloma.
abstract: 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.
authors.affiliation: Department of Cellular Biotechnology and Haematology, Sapienza University of Rome, Rome, Italy. petrucci@bce.uniroma1.it
authors.forename: Maria T
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.forename: Adriana
authors.initials: A
authors.lastname: Teixeira
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Igor W
authors.initials: IW
authors.lastname: Blau
authors.forename: Johannes
authors.initials: J
authors.lastname: Drach
authors.forename: Ralf
authors.initials: R
authors.lastname: Angermund
authors.forename: Nathalie
authors.initials: N
authors.lastname: Allietta
authors.forename: Esther
authors.initials: E
authors.lastname: Broer
authors.forename: Vivien
authors.initials: V
authors.lastname: Mitchell
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005060:Europe; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000601:surgery; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D016879:Salvage Therapy; D013792:Thalidomide / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone