Efficacy and safety of bisphosphonates therapy for patients diagnosed with multiple myeloma: A comprehensive Bayesian network meta-analysis.

Abstract

e19526 Background: Multiple myeloma (MM) is a hematologic malignancy characterized by clonal plasma cell proliferation in the bone marrow, leading to skeletal complications such as osteolytic lesions, fractures, and pain. Bisphosphonates, including zoledronic acid, pamidronate, and ibandronate, are widely used to manage these bone-related events. However, the comparative efficacy and safety of these therapies remain unclear, necessitating this analysis to optimize treatment strategies. Methods: A Bayesian network meta-analysis was conducted on 18 randomized controlled trials (RCTs) involving 3,431 patients. The primary outcomes included overall survival (OS), progression-free survival (PFS), vertebral fractures, non-vertebral fractures, and skeletal-related events (SREs). Relative risks (RRs) with 95% credible intervals (CrIs) were estimated and treatments were ranked using Surface Under the Cumulative Ranking Curve (SUCRA) values, with control as the reference. Results: For OS, etidronate ranked highest (RR = 1.22, 95% CrI: 0.22–2.54, SUCRA: 74.62%), followed by control (SUCRA: 69.38%), pamidronate (RR = 0.80, 95% CrI: 0.37–1.38, SUCRA: 41.23%), and clodronate (RR = 0.78, 95% CrI: 0.28–1.38, SUCRA: 38.04%), with zoledronate ranking the lowest (SUCRA: 10.47%). Pamidronate ranked highest for PFS (RR = 1.20, 95% CrI: 0.36–4.07, SUCRA: 78.12%) and vertebral fractures (RR = 0.63, 95% CrI: 0.16–1.25, SUCRA: 77.16%). Clodronate was most effective for non-vertebral fractures (RR = 0.64, 95% CrI: 0.19–1.57, SUCRA: 83.78%). Zoledronate ranked highest for SREs (RR = 0.42, 95% CrI: 0.10–0.81, SUCRA: 88.88%). Conclusion: This analysis highlights etidronate as the most effective for OS, pamidronate for PFS and vertebral fractures, and zoledronate for SREs. These findings emphasize the value of bisphosphonates in managing myeloma bone disease, providing evidence to guide individualized treatment decisions. Outcome Treatment RR (95% CrI) SUCRA (%) Overall Survival (OS) Etidronate 1.22 (0.22–2.54) 74.62 Control Reference 69.38 Ibandronate 1.04 (0.29–3.71) 66.25 Pamidronate 0.80 (0.37–1.38) 41.23 Clodronate 0.78 (0.28–1.38) 38.04 Progression-Free Survival (PFS) Pamidronate 1.20 (0.36–4.07) 78.12 Control Reference 70.23 Clodronate 0.53 (0.09–2.66) 27.91 Zoledronate 0.60 (0.33–1.08) 23.75 Vertebral Fracture Pamidronate 0.63 (0.16–1.25) 77.16 Clodronate 0.67 (0.22–1.56) 70.45 Ibandronate 1.01 (0.21–4.86) 30.26 Control Reference 22.12 Non-Vertebral Fracture Clodronate 0.64 (0.19–1.57) 83.78 Control Reference 47.75 Ibandronate 1.22 (0.26–5.86) 35.76 Pamidronate 1.30 (0.24–4.62) 32.71 Skeletal-Related Events (SREs) Zoledronate 0.42 (0.10–0.81) 88.88 Pamidronate 0.71 (0.26–1.89) 55.26 Etidronate 0.70 (0.12–4.08) 54.22 Clodronate 0.76 (0.14–4.13) 49.47