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Background: First line therapy for hypercalcemia of malignancy (HCM) includes cancer directed treatment and bisphosphonate therapy. Denosumab is effective in bisphosphonate-refractory HCM (BR-HCM), approved for treatment with dosing schedule at 1, 8, 15, and 29 days and then monthly. Clinical Case: We present the case of a 64 year-old man with Stage IIIA squamous cell lung carcinoma diagnosed 5/2019 with corrected serum calcium (CSC) of 11.2 mg/dL (8.4–10.2) at presentation. Prior to treatment, he developed symptomatic CSC 14.0 mg/dL, treated with IV pamidronate 90mg and IV fluids (IVF) 6/28/2019 with improvement to CSC 9.7 mg/dL. Hypercalcemia recurred 8/2019 while undergoing radiation therapy with CSC 14.7 mg/dL, phosphorus 2.5 mg/dL (2.7–4.5), PTH 7 pg/mL (15–65), PTHrP 2.2 pmol/L (&amp;lt;2.0), 25-OH vitamin D 30.16 ng/mL (30–100), and 1,25-OH2 vitamin D 98.7 pg/mL (19.9–79.3). He was treated with IVF and 4mg zoledronic acid (ZA) on 8/20 and 8/29/2019. CSC normalized 9/30/2019 and he subsequently received three cycles of pembrolizumab 11/25/2019 to 1/6/2020, discontinued for associated pneumonitis He again developed HCM 6/5/2020 with CSC 12.6 mg/dL. He was treated with ZA 4mg on 6/16 and 6/29/2020 with persistent, symptomatic hypercalcemia to 13.7 mg/dL 7/9/2020 with ongoing confusion, constipation, and lethargy. Endocrinology was consulted 7/9/2020 and initiated IVF, calcitonin SQ 4U/kg q12h for 48 hours, and prednisone 30mg daily for 5 days. Chemotherapy was initiated 7/14/2020. CSC remained stable &amp;lt;11.5 mg/dL until 8/3/2020 with recurrent calcium to 13.0 mg/dL despite cancer-directed therapy. He was then given 120mg SQ denosumab on 8/7/2020. CSC improved to 10.6 mg/dL on 8/11/2020 and has remained &amp;lt;11 mg/dL at 70 days after a single dose of denosumab. Conclusion: Denosumab was approved for BR-HCM with a complex treatment schedule based on a single-arm study of 33 patients, of whom 39% had treatment-related adverse events.1 We present a case of successful management of BR-HCM with a single dose of 120mg denosumab with CSC &amp;lt;11.5 mg/dL at day 4 after treatment and persistent control of calcium at day 70 without further treatment. Further investigation is warranted to determine the most effective treatment schedule of denosumab for BR-HCM to reduce adverse events including hypocalcemia and overtreatment. References: 1. Hu MI, Glezerman IG, Leboulleux S, et al. Denosumab for treatment of hypercalcemia of malignancy. J Clin Endocrinol Metab. 2014 Sep;99(9):3144–52

Single Dose of Denosumab Effective for Management of Bisphosphonate-Refractory Hypercalcemia of Malignancy Related to Non-Small Cell Lung Cancer