Meta-analysis of the efficacy and safety of bortezomib re-treatment in patients with multiple myeloma

Clin Lymphoma Myeloma Leuk. 2014 Oct;14(5):380-8. doi: 10.1016/j.clml.2014.03.005. Epub 2014 Jun 11.

Abstract

Introduction: 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.

Patients and 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%).

Conclusion: 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.

Keywords: Meta-regression analysis; Overall response rate; Random-effect model; Refractory; Relapsed.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Boronic Acids / administration & dosage
  • Boronic Acids / adverse effects
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Clinical Trials as Topic
  • Disease-Free Survival
  • Hematologic Diseases / chemically induced
  • Humans
  • Molecular Targeted Therapy* / adverse effects
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / enzymology
  • Neoplasm Proteins / antagonists & inhibitors*
  • Peripheral Nervous System Diseases / chemically induced
  • Pneumonia / etiology
  • Proteasome Inhibitors / administration & dosage
  • Proteasome Inhibitors / adverse effects
  • Proteasome Inhibitors / therapeutic use*
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • Recurrence
  • Retrospective Studies
  • Salvage Therapy* / adverse effects
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Boronic Acids
  • Neoplasm Proteins
  • Proteasome Inhibitors
  • Pyrazines
  • Bortezomib