Ghada El-Hajj Fuleihan(Chair), Gregory A. Clines, Mimi I. Hu, Claudio Marcocci, M. Hassan Murad, Thomas Piggott, Catherine Van Poznak, Joy Y. Wu, Matthew T. Drake (Co-Chair)
The 2022 guideline on management of hypercalcemia of malignancy:
Focuses on the treatment of adults with hypercalcemia of malignancy
Emphasizes controlling hypercalcemia and preventing its recurrence
Hypercalcemia of malignancy (HCM), a condition associated with high morbidity and mortality, is the most common metabolic complication of malignancies.
All adults with HCM should receive treatment with denosumab (Dmab) or an intravenous (IV) bisphosphonate (BP).
Adults with calcitriol-mediated HCM should first be treated with glucocorticoids, with the addition of Dmab or an IV BP if glucocorticoid therapy is insufficient.
List of Recommendations
Adults with hypercalcemia of malignancy
Recommendation 1:In adults with hypercalcemia of malignancy (HCM), we recommend treatment with an intravenous (IV) bisphosphonate (BP) or denosumab (Dmab) compared with management without an IV BP or Dmab. (1⊕◯◯◯)
Recommendation 2: In adults with hypercalcemia of malignancy (HCM), we suggest treatment with denosumab (Dmab) over an intravenous (IV) bisphosphonate (BP). (2⊕◯◯◯)
Recommendation 3: In adults with severe hypercalcemia of malignancy (HCM) (serum calcium [SCa]>14 mg/dL [3.5 mmol/L]), we suggest a combination of calcitonin and an intravenous (IV) bisphosphonate (BP) or denosumab (Dmab) as initial treatment, compared with only IV BP or Dmab. (2⊕◯◯◯)
Remark:
Calcitonin treatment should be limited to 48-72 hours due to tachyphylaxis.
Refractory and recurrent hypercalcemia
Recommendation 4: In adults with refractory/recurrent hypercalcemia of malignancy (HCM) on an intravenous (IV) bisphosphonate (BP), we suggest the use of denosumab (Dmab), compared with management without Dmab. (2⊕◯◯◯)
Hypercalcemia due to calcitriol-associated malignancy
Recommendation 5:In adults with hypercalcemia of malignancy (HCM) from tumors associated with high calcitriol levels, such as lymphomas, who are already receiving glucocorticoid therapy but who continue to have severe or symptomatic hypercalcemia, we suggest the addition of an intravenous (IV) bisphosphonate (BP) or denosumab (Dmab) compared with management without an IV BP or Dmab. (2⊕◯◯◯)
Adults with hypercalcemia due to parathyroid carcinoma
Recommendation 6: In adult patients with hypercalcemia of malignancy (HCM) due to parathyroid carcinoma, we suggest treatment with either a calcimimetic or an intravenous (IV) bisphosphonate (BP) or denosumab (Dmab). (2⊕◯◯◯)
Remarks:
In adult patients with parathyroid carcinoma, surgery should be considered when feasible, once control of severe hypercalcemia has been achieved; however, surgical considerations were outside of the scope of this guideline.
Depending on the clinical situation and severity of hypercalcemia, an IV BP or Dmab may be useful prior to calcimimetic initiation. In adults with mild hypercalcemia and related symptoms, we suggest starting therapy with calcimimetics; conversely adults with moderate-to severe hypercalcemia and related symptoms, an IV BP or Dmab should be the initial therapy.
This recommendation considers the more rapid onset of action of an IV BP or Dmab, and generally better tolerability profile, as compared to a calcimimetic (as adverse events are common with increasing calcimimetic doses).
Recommendation 7:In adult patients with hypercalcemia of malignancy (HCM) due to parathyroid carcinoma not adequately controlled despite treatment with a calcimimetic, we suggest the addition of an intravenous (IV) bisphosphonate (BP) or denosumab (Dmab) compared with management without an IV BP or Dmab. (2⊕OOO)
Recommendation 8: In adult patients with hypercalcemia of malignancy (HCM) due to parathyroid carcinoma who are not adequately controlled on an intravenous (IV) bisphosphonate (BP) or denosumab (Dmab) therapy, we suggest the addition of a calcimimetic compared with management without a calcimimetic. (2⊕OOO)
