Abstract
BackgroundSevere hypercalcemia is often associated with uncontrolled malignancy through several mechanisms. However, calcitriol-mediated hypercalcemia is a rare etiology for advanced solid tumors.Case presentationWe 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.ConclusionThis case suggests calcitriol-mediated hypercalcemia as a novel immune-related adverse event.
Highlights
Severe hypercalcemia is often associated with uncontrolled malignancy through several mechanisms
He remains on nivolumab maintenance therapy with ongoing partial response of his disease, no recurrent hypercalcemia, and no further immunotherapy-related adverse events to date
We report the first-known case of calcitriol-mediated hypercalcemia associated with immunotherapy
Summary
Severe hypercalcemia is often associated with uncontrolled malignancy through several mechanisms. Conclusion: This case suggests calcitriol-mediated hypercalcemia as a novel immune-related adverse event. In such rare cases involving solid tumors, alternative mechanisms for explaining calcitriol-mediated hypercalcemia must be explored, when therapies themselves may play a role, such as in the case described below.
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