Bortezomib for the treatment of multiple myeloma: A systematic review and meta-analysis

Background: Multiple myeloma is a plasma cell malignancy accounting for approximately 1% of cancers diagnosed and 12% of haematological malignancies. The first-in-class proteasome inhibitor, bortezomib, is commonly used in all myeloma disease settings. We conducted a systematic review and meta-analysis to evaluate the accumulated clinical evidence of bortezomib treatment of myeloma. Aims: To assess the clinical benefits and side effects of bortezomib compared to other therapies, doses, administration methods and treatment schedules. Primary objectives were to assess effects of bortezomib on overall survival (OS) and progression-free survival (PFS). Secondary objectives included response rates (RR), adverse events (AE), treatment-related death (TRD) and health-related quality of life (HRQoL). Methods: We searched MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE (till end of Nov 2014), conference proceedings and clinical trial registries for randomised controlled trials (RCTs). Two review authors independently extracted outcomes data and assessed risk of bias. Hazard ratios (HR) and their confidence intervals (CI) were extracted for OS and PFS and Odds Ratios (OR) for RRs, AEs and TRD. Trial authors were contacted if summary statistics were missing. Log-rank statistics were estimated if not available. Results: Sixteen relevant RCTs involving 5630 patients were identified and 12 trials included in the meta-analysis. Four trials of different doses, administration and treatment schedules were reviewed qualitatively. Overall risk of bias was considered to be generally low. We estimated OS benefit from 4118 patients (Peto OR=0.77 (95% CI: 0.69 to 0.86, P