ODP068 A Case Report of Nivolumab Associated Hypercalcemia

INTRODUCTION: Nivolumab is a human immunoglobulin G4 (IgG4) antibody which binds to programmed cell death receptor-1 (PD-1) and blocks the binding of PD-1 to either the PD-ligand 1 (PD-L1) or PD-L2 expressed on the surface of cancer cells. It has been approved for the treatment of melanoma, non-small cell lung cancer, renal cell carcinoma etc. Various endocrine immune-related adverse events including thyroiditis, hyper- and hypothyroidism, hypophysitis and type 1 diabetes has been described. We report a case of Nivolumab associated hypercalcemia. CASE PRESENTATION: 67-year-old female with history of CKD stage 3 with secondary hyperparathyroidism, melanoma of right ankle was admitted after one month of receiving the first dose of Nivolumab for her melanoma. She had altered mentation with elevated corrected calcium of 15.94(8.4-10.2) mg/dl. Prior calcium levels were in low to normal range, eGFR was 13, creatinine elevated at 3.4 (0.57-1.11) mg/dl, PTH 84 (10-65) pg/ml, 25 OH vitamin D 54 (30-74) ng/ml, Phosphorus normal, Magnesium normal, 1,25-OH vitamin D was elevated at 103(18-72) pg/ml, PTHrp normal, normal SPEP, normal TSH, no history of fractures, normal DXA, no history of kidney stones, not on any calcium supplements, not on thiazide or lithium. Chest x ray and NM full body PET CT did not show any evidence of granulomatous disease except for recurrence and metastasis of melanoma in right thigh, calf, and ankle. No family history of kidney stones or hypercalcemia. Patient was treated with IV fluids and Calcitonin. Her calcium quickly improved to 9.9 within 48 hours. Within 3 weeks of discharge, she was readmitted for elevated calcium of 14.4 mg/dl, creatinine 2.29 mg/dl, eGFR 21, PTH 96 pg/ml, Mg 1.8 (1.6-2.6) mg/dl. She was treated with IV fluids and calcitonin and calcium normalized within 48 hours. Parathyroid scan did not show any parathyroid adenoma. She was started on prednisone for possible Nivolumab associated immune adverse reaction. She was also briefly treated with cinacalcet which was discontinued. Prednisone was tapered and then stopped over the course of 6 weeks. Calcium remains normal. PTH remains slightly elevated which is thought to be due to secondary hyperparathyroidism from CKD. Normal cortisol level. DISCUSSION: This is likely a case of Nivolumab associated hypercalcemia given the onset soon after immunotherapy initiation and improvement with glucocorticoid therapy. Immunotherapy was not resumed after the first dose due to recurrent severe hypercalcemia. The patient is currently under surveillance for melanoma. Calcium level remains normal. Although it is rare, a few cases of Nivolumab associated hypercalcemia have been reported previously. Exact mechanism is not known but it has been speculated that macrophage activation by Nivolumab can cause increased level of 25(OH) D-hydroxylase with increased conversion of 25-OH vitamin D to 1,25-OH vitamin D resulting in calcitriol mediated hypercalcemia. Presentation: No date and time listed