A meta-analysis of the antitumor effect and safety of bisphosphonates in the treatment of multiple myeloma

Background: The objective of this meta-analysis was to determine the effectiveness and safety of bisphosphonates (BPs) for patients with multiple myeloma (MM). Methods: The study included patients with MM, who were randomly allocated to receive either BPs or control. PubMed/Medline, Embase, the Cochrane Database of Systematic Reviews (CDSR), and the Cochrane Central Register of Controlled Trials were searched up to January 2014, and only published trials were included in the analysis. There was no language restriction. The results were analyzed using RevMan 5.2 software, which was provided by Cochrane Collaboration. Results: Six randomized controlled trials (RCTs) covering 1951 patients with MM were included in the analysis. The clodronate subgroup showed superior progression-free survival compared to the other groups. The pooled hazard ratio (HR) was 0.57 [95% confidence interval (CI) 0.33-0.99, P = 0.04]. Regarding overall survival (OS), only zoledronic acid showed a clear advantage (HR = 0.51, 95% CI 0.33-0.77, P = 0.002) All BPs were effective at reducing skeletal-related events (SREs). The pooled risk ratios for the outcome of SREs were 0.72 (95% CI: 0.62-0.84, P < 0.0001) for the clodronate subgroup, 0.66 (95% CI: 0.48-0.91, P = 0.007) for the pamidronate subgroup, and 0.65 (95% CI: 0.46-0.91, P = 0.01) for the zoledronic acid subgroup. Several adverse events (AEs) were mentioned in the included RCTs; however, the pooled results showed no statistically significant differences between the BP groups and the control. Conclusions: The present meta-analysis demonstrated that zoledronic acid may improve the OS of patients with MM. All BPs markedly decreased SREs and were tolerated well.