Despite i.v. bisphosphonates, including pamidronate and zoledronate, representing the established agents used to reduce calcium levels, a proportion of patients with hypercalcemia either fail to respond to such treatments or relapse following their use.
We present a case of hypercalcaemia refractory to conventional treatments that was treated with the use of the human MAB denosumab.
A 70-year-old male presented to the emergency department following shortness of breath due to an underlying mesothelioma requiring palliative treatment. During the admission, the patient was noted to have an elevated corrected calcium level of 3.31 mmol/l (range: 2.12.7 mmol/l) which was presumed to be hypercalcaemia of malignancy. Despite improving to 2.7 mmol/l with i.v. fluids and 30 mg of i.v. pamidronate, levels increased to 3.12 mmol/l within 3 days. With an adequate eGFR of >90 ml/min, 90 mg of i.v. pamidronate was then used to correct his calcium level but only provided a temporary benefit. Biochemical analysis of the level of parathyroid hormone revealed it was elevated at 20.7 pmol/l (range:1.66.9 pmol/l), thereby suggesting that this was primary hyperparathyroidism and not hypercalcemia of malignancy. Although i.v. zoledronate was then tried, within a period of a week, the patients calcium levels had increased to 3.08 mmol/l. Given the delay in obtaining approval for cinacalcet for primary hyperparathyroidism, the recalcitrant nature of the patients hypercalcaemia and the patients deteriorating condition, 60 mg of s.c. denosumab was trialled off-label. The patients corrected calcium levels fell to 2.76 mmol/l and remained within normal limits for over a month. The patient however succumbed to his malignancy and unfortunately passed away.
Conclusion: Denosumab may provide another therapeutic option for the management of hypercalcaemia refractory to i.v. bisphosphonate therapy. There are ongoing studies which will give us more evidence over the next few years.