6542 Burosumab In Unresectable/Unidentifiable Tumor-Induced Osteomalacia

Abstract Disclosure: Y. Der: None. S.K. Chaubey: None. A.K. Sinha: None. Introduction/Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, typically arising from small, benign, slow-growing mesenchymal tumors, that secrete fibroblast growth factor (FGF23) and other phosphaturic proteins. It is characterized by hypophosphatemia, phosphaturia, reduced serum 1,25 dihydroxyvitamin D and bone demineralization. While complete resection of the causative tumor is the curative approach, unresectable or unidentifiable cases necessitate medical therapy with oral phosphate and calcitriol. Unfortunately, this option proves suboptimal, plagued by low compliance due to intolerable gastrointestinal side effects. A recent stride in treatment includes the approval of burosumab, an anti-FGF-23 monoclonal antibody, for TIO in the USA. Clinical Case: We report a perplexing TIO case where the underlying tumor remains elusive to-date. The patient, a 41-year-old former Filipino national swimmer, presented at the age of 35, wheelchair-bound, with a four-year history of progressive functional decline, secondary to diffuse osteomuscular pain and multiple fractures. Investigations revealed hypophosphatemia (0.28mmol/L; reference range: 0.75-1.5), phosphaturia, elevated ALP, low 1,25 dihydroxyvitamin D, and elevated peak FGF23 at 217ng/L (reference range: 23.2-95.4). Despite exhaustive imaging studies and stepwise venous sampling, tumor localization proved elusive. The patient experienced improvement in overall mobility and functional status on regular phosphate and calcitriol supplements. Cinacalcet was later added to reduce secondary hyperparathyroidism, FGF levels, and the need for phosphate supplements. Nevertheless, her chronic pain and limited mobility persisted, along with supplementation-associated gastrointestinal symptoms. The ionized calcium and phosphate remained low/low normal. In September 2023, the patient was commenced on subcutaneous burosumab via special access scheme, initially at 0.5mg/kg/month, subsequently uptitrated to the current 1mg/kg/month dosage. Remarkable improvements in pain and physical performance ensued, as evidenced by functional assessment and questionnaire tools. Serum phosphate levels are currently maintaining at 0.8mmol/L, with the most recent FGF level following her third burosumab injection improved to 88.4ng/L. Currently, four months into treatment, no side effects have been reported, and all previous supplementation and cinacalcet has been discontinued. Clinical Lessons/Conclusions: To our knowledge, this represents the first TIO case in Australia treated with burosumab. This case highlights favorable effects, including serum phosphate normalization and significant improvements in mobility, pain and quality of life. Thus, this case underscores the potential of burosumab in managing unresectable or unidentifiable TIO cases. Presentation: 6/1/2024