A case series of hypercalcemia associated with pembrolizumab therapy: evidence for a calcitriol-mediated mechanism

TL;DR

Two patients experienced hypercalcemia from pembrolizumab therapy, which was resolved after stopping the drug and using supportive treatments.

Contribution

The paper presents evidence for a calcitriol-mediated mechanism in pembrolizumab-induced hypercalcemia.

Findings

Two cases of pembrolizumab-induced hypercalcemia were successfully treated with discontinuation and supportive therapies.

Hypercalcemia occurred independently of parathyroid hormone (PTH) levels.

The findings highlight the importance of recognizing immune checkpoint inhibitors as a cause of hypercalcemia.

Abstract

Immune checkpoint inhibitors enhance antitumor immunologic activity by blocking interaction between inhibitory immune checkpoint receptors. Pembrolizumab blocks the programmed cell death (PD-1) receptor and has been effective in the treatment of many malignancies. While many immune-related endocrinologic adverse effects have been described, immunotherapy-induced hypercalcemia is a rare adverse effect. We present 2 cases of patients who developed pembrolizumab-induced hypercalcemia. Both patients achieved resolution of hypercalcemia with discontinuation of pembrolizumab along with treatment with intravenous fluids, calcitonin, anti-resorptive therapy with either bisphosphonate or denosumab, and glucocorticoid therapy. These cases demonstrate the importance of recognizing immune checkpoint inhibitors as potential causes of parathyroid hormone (PTH)-independent hypercalcemia.