Hypercalcaemia as an immune-related adverse event secondary to ipilimumab and nivolumab therapy in a patient with metastatic renal cell carcinoma

BMJ Case Rep. 2026 Feb 10;19(2):e266771. doi: 10.1136/bcr-2025-266771.

Abstract

We report a case of severe hypercalcaemia after a single cycle of a combination therapy of ipilimumab and nivolumab. Initial evaluation ruled out common causes, including bone metastases, parathyroid hormone/parathyroid hormone-related protein elevation and paraproteinaemia. Her serum 1,25-dihydroxyvitamin D (calcitriol) levels were significantly elevated following the first immunotherapy cycle. Hypercalcaemia responded only to glucocorticoid therapy, with normalisation of serum calcium and calcitriol levels. Recurrence of hypercalcaemia after glucocorticoid discontinuation and subsequent resolution with glucocorticoid re-initiation strongly supported a calcitriol-mediated mechanism, most likely as an immune-related effect of ipilimumab and nivolumab.

Keywords: Calcium and bone; Immune Checkpoint Inhibitors; Immunological products and vaccines; Renal system.

Publication types

  • Case Reports

MeSH terms

  • Antineoplastic Agents, Immunological* / adverse effects
  • Calcitriol / blood
  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / secondary
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Hypercalcemia* / blood
  • Hypercalcemia* / chemically induced
  • Hypercalcemia* / drug therapy
  • Ipilimumab* / administration & dosage
  • Ipilimumab* / adverse effects
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / pathology
  • Middle Aged
  • Nivolumab* / adverse effects

Substances

  • Nivolumab
  • Ipilimumab
  • Antineoplastic Agents, Immunological
  • Glucocorticoids
  • Calcitriol