Hypercalcemia Secondary to Calcitriol Production From Dual Combination Immunotherapy in Pulmonary Metastatic Melanoma

Nivolumab and ipilimumab are immunotherapy agents recommended for the treatment of metastatic melanoma. A rare adverse effect of these agents is hypercalcemia. The mechanism of immunotherapy-mediated hypercalcemia is thought to be due to ectopic calcitriol production from activated macrophages, similar to sarcoidosis. We present a case of a 76-year-old female with metastatic melanoma who developed severe hypercalcemia after completing a cycle of combined nivolumab and ipilimumab therapy. After other common causes of hypercalcemia in malignancy were ruled out, the decision was made to aggressively treat her hypercalcemia while inpatient and hold immunotherapy at discharge. Since holding immunotherapy, she has not had a repeat occurrence of hypercalcemia. This case stresses the importance of including immunotherapy adverse effects in the differential diagnosis for hypercalcemia in malignancy.