What are the American Society of Clinical Oncology (ASCO) clinical practice guidelines governing bisphosphonate therapy for multiple myeloma (MM) patients?

Updated: May 11, 2021
  • Author: Dhaval Shah, MD; Chief Editor: Emmanuel C Besa, MD  more...
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In 2017, the American Society of Clinical Oncology (ASCO) issued an update to its clinical practice guideline on the role of bone-modifying agents in multiple myeloma. [47] ASCO recommendations include the following:

  • For patients with multiple myeloma in whom imaging studies show lytic destruction of bone or compression fracture of the spine from osteopenia, intravenous (IV) pamidronate (90 mg delivered over at least 2 hours) or zoledronic acid (4 mg delivered over at least 15 minutes every 3 to 4 weeks) is recommended. Denosumab is an alternative.
  • In patients with solitary plasmacytoma or smoldering (asymptomatic) or indolent myeloma who have osteopenia but no lytic disease, starting bisphosphonates is not recommended.
  • In patients with monoclonal gammopathy of undetermined significance, starting bisphosphonate therapy is not recommended unless they have osteopenia or osteoporosis.
  • In patients receiving radiation therapy, analgesics, or surgical intervention for fractures or impending fractures, IV pamidronate or zoledronic acid is recommended as an adjunctive treatment. Denosumab is an additional option.
  • In patients with multiple myeloma who have osteopenia (osteoporosis) but no radiographic evidence of lytic bone disease, IV bisphosphonates may be started.

ASCO recommendations for patients with renal impairment include the following:

  • Patients with preexisting mild-to-moderate renal impairment (estimated creatinine clearance, 30 to 60 mL/min) should receive a reduced dosage of zoledronic acid. No changes in infusion time or interval are required.
  • Zoledronic acid is not recommended for use in patients with severe renal impairment. Denosumab may be preferred over zoledronic acid in patients with compromised renal function.
  • Pamidronate 90 mg administered over 4 to 6 hours, is recommended for patients with extensive bone disease and existing severe renal impairment (serum creatinine level > 3.0 mg/dL [265 µmol/L] or an estimated creatinine clearance < 30 mL/min). In patients with preexisting renal impairment, consider reducing the initial pamidronate dose. Infusion times less than 2 hours with pamidronate or less than 15 minutes with zoledronic acid should be avoided.

ASCO recommendations regarding duration of therapy include the following:

  • Continuing bone-targeted treatment for up to 2 years is suggested. Consider less frequent dosing \in patients with responsive or stable disease.
  • In patients who do not have active myeloma and are on maintenance therapy, consider a 3-month interval of bisphosphonate administration.
  • For patients in whom bisphosphonates were withdrawn after 2 years and relapse with new-onset skeletal-related events occurs, the drug should be resumed.
  • Denosumab should not be stopped abruptly, given its reversible mechanism of action.

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