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Introduction Denosumab inhibits receptor activator of nuclear factor k-B ligand and is approved to treat giant cell tumor of bone (GCTB). Rebound hypercalcemia is a rare complication of denosumab withdrawal in pediatrics which is not reported in adults. We describe severe hypercalcemia in an adult with metastatic GCTB associated with denosumab withdrawal that was complicated by cancer treatment directed against fibroblast growth factor receptors (FGFR). Clinical case A 29-year-old male with metastatic GCTB was admitted for severe hypercalcemia, acute kidney injury (AKI) and fatigue, constipation and poor appetite. An extraosseous GCT of abdominal wall had been resected and monthly denosumab was started a year later for bone metastases. Molecular analysis showed FGFR-1 rearrangement and he was enrolled in a clinical trial using an FGFR inhibitor (FGFRi) against FGFR1, 2 and 3. The patient received 8 doses of denosumab before the FGFRi was started and denosumab was held for 3 months as the FGFRi dose was increased. After 80 days of the FGFRi, he had an increased serum phosphorus concentration of 7.4mg/dL (2.5-4.5mg/dL), increased 1,25 dihydroxyvitamin D at 164pg/mL (18-64pg/mL) and corrected serum calcium concentration of 8.9mg/dL (8.4-10.2mg/dL). The FGFRi was held for hyperphosphatemia; one week later he presented with severe hypercalcemia (17.0mg/dL) with suppressed parathyroid hormone 13.8pg/mL (15-65pg/mL) and 1,25dihydroxyvitamin D Conclusion This case illustrates the severe, rapid nature of hypercalcemia associated with denosumab withdrawal when used to treat an extreme osteolytic tumor: GCTB. It also illustrates potential interactions when denosumab is discontinued in the setting of other drugs which alter mineral metabolism, such as the phosphate and vitamin D pathway regulated by the FGFRs. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m. |
