From the Guidelines
The treatment for hypercalcemia in multiple myeloma should prioritize aggressive hydration with intravenous fluids, followed by bisphosphonate therapy, with zoledronic acid being the preferred bisphosphonate, as recommended by the NCCN guidelines 1.
Key Components of Treatment
- Aggressive hydration with intravenous fluids, typically normal saline at 200-300 mL/hour
- Bisphosphonate therapy, with zoledronic acid (4 mg IV over 15-30 minutes) being the preferred option due to its efficacy in reducing hypercalcemia and its preference by the NCCN panel 1
- Calcitonin (4-8 IU/kg SC every 12 hours) may be added for severe cases to provide rapid but short-term calcium reduction
- Loop diuretics like furosemide should only be used after adequate hydration is achieved
- Corticosteroids such as dexamethasone (40 mg daily for 4 days) help reduce tumor burden and calcium release from bone ### Additional Considerations
- The definitive treatment involves anti-myeloma therapy with regimens containing proteasome inhibitors (bortezomib), immunomodulatory drugs (lenalidomide), and dexamethasone
- Hemodialysis may be necessary for severe, refractory hypercalcemia or in patients with renal failure
- These interventions work by increasing urinary calcium excretion, inhibiting osteoclast activity, reducing bone resorption, and decreasing tumor burden, thereby addressing the underlying mechanism of hypercalcemia in multiple myeloma, which is excessive bone breakdown due to increased osteoclast activity stimulated by myeloma cells ### Guideline Recommendations
- The NCCN guidelines recommend bisphosphonates (category 1) or denosumab for all patients receiving therapy for symptomatic multiple myeloma regardless of documented bone disease 2
- Denosumab is preferred by the NCCN MM Panel in patients with renal disease 2
From the FDA Drug Label
Zoledronic acid injection is a bisphosphonate indicated for the treatment of: Hypercalcemia of malignancy. Patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. 4 mg as a single-use intravenous infusion over no less than 15 minutes. 4 mg as retreatment after a minimum of 7 days.
The treatment for hypercalcemia in multiple myeloma is Zoledronic acid injection at a dose of 4 mg as a single-use intravenous infusion over no less than 15 minutes. The dose can be repeated after a minimum of 7 days.
- Key points:
- Zoledronic acid injection is indicated for hypercalcemia of malignancy.
- It is used in conjunction with standard antineoplastic therapy for patients with multiple myeloma.
- The recommended dose is 4 mg as a single-use intravenous infusion.
- The dose can be repeated after a minimum of 7 days. 3
From the Research
Treatment Options for Hypercalcemia in Multiple Myeloma
- The treatment of hypercalcemia of malignancy consists of enhancing renal calcium excretion, mostly through hydration with isotonic fluids and the use of antiresorptive therapies 4.
- Intravenous zoledronic acid is currently the first-line treatment for hypercalcemia in multiple myeloma 4.
- Subcutaneous denosumab is used for bisphosphonate-refractory hypercalcemia and in patients with renal failure 4.
- Bisphosphonates, potent inhibitors of bone resorption, are recommended as the most effective therapy and have been approved for treatment of hypercalcemia in myeloma 5.
Management and Diagnosis
- Hypercalcemia arises in the advanced stage of myeloma due to marked increase in osteoclastic bone resorption by local factors in the bone marrow, and is among the most serious complications in myeloma 5.
- Early detection by serum calcium levels and treatment of hypercalcemia is important, although its clinical symptoms are difficult to distinguish from those in other underlying complications 5.
- Evaluation of patients with possible multiple myeloma includes measurement of serum calcium levels, among other tests 6.
Novel Therapies
- Novel therapies for refractory disease include denosumab, a monoclonal antibody against the receptor activator of nuclear factor κB ligand, and the calcimimetic cinacalcet 7.
- Anti-PTHrP antibodies have been successfully deployed in animal models of disease 7.
Prognosis
- Despite the efficacy of the above therapies, hypercalcemia of malignancy portends an ominous prognosis, indicating advanced and often refractory cancer with survival on the order of months 7.