MON-786 Fracture Rates After Immunotherapy: Under-recognized And Under-treated

Abstract Disclosure: J. Chen: Immunovant. H. Magon: None. J. Coyle: None. C. Pike: None. J. Muralidharan: None. S.H. Kim: Novo Nordisk, Morphic Medical, TeCure. Y. Motlaghzadeh: None. D. Sellmeyer: None. J.Y. Wu: None. Introduction: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment. ICIs are believed to induce a pro-inflammatory state and promote RANKL-mediated bone loss. Evidence suggests increased fracture risk and elevated bone turnover in ICI-treated patients. This study evaluates the incidence of fractures in patients before and after ICI treatment. Additionally, we examine the proportion of patients who sustained a fracture and subsequently initiated bone-directed therapy within one year of the event. Methods: We conducted a case series study using the Apollo Dataset from the Atropos Health Evidence Network, which includes deidentified electronic health record data across the United States. We identified patients over 50 years of age who received ICIs from 2010-2024 and had at least 5 years of observable data before and after receiving ICI. ICD diagnostic codes were used to identify fracture events. If a fracture code was recorded within six months of another fracture code affecting the same anatomical area, it was not counted as a separate fracture. We excluded patients who received bone-directed medications prior to fracture event. We compared the incidence rates of fracture in the 5 years before ICI initiation to the 5 years after ICI initiation. In patients who had a fracture event, we assessed if they received bone directed therapy within 1 year following the fracture event. Results: We identified 928 patients who received ICI and had complete data for the five years pre-ICI and post-ICI (mean age 67.9 years, 40.1% female, 73% White). Fractures occurred in 56 patients (6%) pre-ICI and in 132 patients (14.2%) post-ICI. The fracture incidence risk ratio (IRR) post-ICI was 3.13 (p < 0.001). Among patients who experienced a fracture, only 17.4% received bone-directed therapy within one year of the fracture event. Rib fractures were the most common fracture site before ICI therapy (35.7%), while vertebral fractures were the most common fracture site after ICI initiation (41.6%). Most fractures (53.7%) occurred within the first two years after receiving ICI. There was increased oral glucocorticoids use (pre-ICI period 14.2% vs. post-ICI period 32.5%) and a higher prevalence of bone metastases (pre-ICI period 14.3% vs. post-ICI period 23.9%) after immunotherapy. Conclusion: Our findings suggest that patients who receive ICI are at increased risk of fracture, yet the majority do not receive treatment within a year of the event. This retrospective study is limited by possible fracture misclassification, lack of bone mineral density data, and the inability to fully account for the effects of glucocorticoid therapy on fracture risk. However, it highlights the need for further investigation into the underlying mechanisms contributing to fracture risk amongst patients who receive ICI. Presentation: Monday, July 14, 2025