title: Meta-analysis of the efficacy and safety of bortezomib re-treatment in patients with multiple myeloma.
abstract: BACKGROUND
  Bortezomib is administered for a finite course; thus, patients might remain sensitive to bortezomib-based therapy at relapse. We report a meta-analysis of bortezomib-based retreatment in relapsed/refractory myeloma.
  
  
  METHODS
  A systematic literature review identified studies of bortezomib-based retreatment in relapsed/refractory myeloma. Proportions of bortezomib-refractory patients and additional prognostic factors were extracted and used in weighted stratified analyses of TTP and OS. Random-effect pooled estimates were calculated for overall response rate (ORR) and rates of common AEs.
  
  
  RESULTS
  Twenty-three studies (n = 1051 patients) were identified. Bortezomib was administered intravenously in all studies. Across studies in which data were available, pooled, weighted average ORR was 39.1% (95% confidence interval, 30.8%-47.4%), and pooled, weighted average median TTP and OS were 7.5 and 16.6 months, respectively. Patients with fewer previous therapies (≤ 4) and relapsed (not refractory) patients achieved higher ORRs, of 43.4% and 57.2%, respectively. Random-effects meta-regression analysis confirmed that relapsed patients were associated with a higher ORR by 28 to 41 percentage points versus refractory patients. In relapsed patients, median TTP and OS were 8.5 and 19.7 months, respectively. Common Grade 3/4 AEs included thrombocytopenia (35%), neutropenia (15%), anemia (14%), pneumonia (10%), and peripheral neuropathy (3%).
  
  
  CONCLUSIONS
  Based on these findings, bortezomib retreatment is well tolerated and appears efficacious in relapsed patients. In an era of new and emerging treatment options for relapsed and/or refractory myeloma, these data indicate that bortezomib retreatment might be a highly effective option in previously treated patients.
authors.affiliation: California Pacific Medical Center, Sutter Health, San Francisco, CA. Electronic address: leroy@alum.MIT.edu.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Knopf
authors.affiliation: Analysis Group, Inc, Boston, MA.
authors.forename: Mei Sheng
authors.initials: MS
authors.lastname: Duh
authors.affiliation: Groupe d'analyse, Ltée, Montreal, Quebec, Canada.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Lafeuille
authors.affiliation: Groupe d'analyse, Ltée, Montreal, Quebec, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gravel
authors.affiliation: Groupe d'analyse, Ltée, Montreal, Quebec, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lefebvre
authors.affiliation: Millennium: The Takeda Oncology Company, Cambridge, MA.
authors.forename: Liviu
authors.initials: L
authors.lastname: Niculescu
authors.affiliation: Millennium: The Takeda Oncology Company, Cambridge, MA.
authors.forename: Abbie
authors.initials: A
authors.lastname: Ba-Mancini
authors.affiliation: Millennium: The Takeda Oncology Company, Cambridge, MA.
authors.forename: Esprit
authors.initials: E
authors.lastname: Ma
authors.affiliation: Millennium: The Takeda Oncology Company, Cambridge, MA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Hematology/Oncology, Tufts Medical Center, Boston, MA.
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Comenzo
mesh_terms: 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; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000201:enzymology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011014:Pneumonia / Q000209:etiology; D061988:Proteasome Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D009363:Neoplasm Proteins; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib
keywords: Meta-regression analysis; Overall response rate; Random-effect model; Refractory; Relapsed