Introduction: Bisphosphonates are widely used in multiple myeloma; but only a randomized clinical have showed that zolendronic acid improved survival as well as reduce the number of bone events. On the other hand, Denosumab, a monoclonal antibody targeting RANKL, appears to reduce skeletal-related events, with no known effect on overall survival in patients with multiple myeloma. The objective of this study is analyze the impact of bisphosphonates treatment and denosumab in a large cohort of patients with multiple myeloma. We used data from TriNetx, a global federated health research platform that includes patients from Europe and US.
Methods: Patients had symptomatic multiple myeloma (ICD-10-CM code C90.0) diagnosed between 2007 and 2022. Comparator cohorts included 3707 MM patients from US and EMEA Collaborative Networks. Analyses have been performed after propensity scoring matching by age, sex, bone fractures in the 3 months prior to diagnosis, bone disease and previous treatment with corticosteroids, calcium and vitamin D. Patients treated with bisphosphonates included: Pamidronate and Zolendronic acid. Kaplan‒Meier analysis was used to estimate survival probabilities, and between-group differences were tested using the log-rank test and hazard ratio.
Results: First of all, we compared patients treated with bisphosphonates vs no treatment (2310 patients in each cohort). Patients treated with bisphosphonates had a significant longer overall survival (OS) (HR 0.748 (0.665-0.841, p< 0.001). (Figure 1). Thereafter, we compared patients treated with denosumab vs no treatment (968 patients in each cohort). Patients treated with denosumab had a significant longer overall survival (OS) (HR 0.708 (0.597-0.839, p< 0.001). (Figure 2). Finally, we compared patients treated with bisphosphonates vs denosumab (960 patients in each cohort). No difference in overall survival (OS) between the two groups of patients (HR 1.070 (0.907-1.263, p=0.271). (Figure 3). Regarding the increased risk of fractures or the need for orthopedic surgery, no differences were found between the patient groups.
Conclusions: This large-scale study based on real-world data confirms the bisphosphonates and denosumab prolong survival in MM, with no differences between them.
