Calcitriol-mediated hypercalcemia as an immune-related adverse event in a patient receiving nivolumab and ipilimumab for metastatic renal cell carcinoma, case report

BACKGROUND: Severe hypercalcemia is often associated with uncontrolled malignancy through several mechanisms. However, calcitriol-mediated hypercalcemia is a rare etiology for advanced solid tumors. CASE PRESENTATION: We report a case of calcitriol-mediated hypercalcemia secondary to immune checkpoint inhibition in a responder with metastatic clear cell renal cell carcinoma (ccRCC). In this case, a 68 year old male with metastatic ccRCC to the liver within 4 months of right radical nephrectomy went on to develop hypercalcemia (12.8 mg/dL) shortly following 2 cycles of nivolumab and ipilimumab. Additional testing showed an elevated calcitriol level (142 pg/mL), low parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) levels, and a normal 25-hydroxyvitamin D level. FDG-PET imaging showed hypermetabolic mediastinal, hilar, and intra-abdominal lymphadenopathy, however the subsequent lymph node biopsy only showed reactive lymphoid cells without malignancy or granuloma. The hypercalcemia was resistant to initial therapy with calcitonin, hydration, and zoledronic acid but quickly responded to high-dose prednisone (1 mg/kg), followed by normalization of calcitriol levels. The patient was rechallenged with nivolumab and ipilimumab which provided a partial response after 4 cycles. He was maintained on low dose prednisone (10 mg daily) leading to a sustained resolution of his hypercalcemia. CONCLUSION: This case suggests calcitriol-mediated hypercalcemia as a novel immune-related adverse event.