Osteoclast inhibitors for multiple myeloma

CT: computed tomography; MM: multiple myeloma; MRI: magnetic resonance imaging; PET/CT: positron emission tomography/computed tomography.

* Advise patients to take daily supplemental calcium (1000 mg daily) and vitamin D (at least 400 IU daily).

¶ We do not offer an osteoclast inhibitor to patients with MM who have no bone lesions identified on cross-sectional imaging (CT, MRI, PET/CT) and have normal bone densitometry, as it is not known whether such patients benefit from this therapy. Other experts offer osteoclast inhibitors to all patients with symptomatic MM, including those without detectable bone involvement.

Δ We suggest treatment be given monthly for a period of at least 2 years. After 2 years, we reassess tolerability and suggest continued treatment, as long as it is well tolerated. Alternatively, it is reasonable to discontinue the osteoclast inhibitor after 2 years in patients with responsive or stable MM with plans to restart the osteoclast inhibitor at MM progression. Our contributors differ in the dosing frequency used for long-term maintenance. For most patients, some contributors administer an osteoclast inhibitor monthly, as long as it is well tolerated. Others increase the dosing interval of zoledronic acid to every 6 to 12 months in patients without active MM (eg, those on maintenance therapy). Dosing interval adjustments are not appropriate for other agents (ie, pamidronate or denosumab). Importantly, if denosumab is discontinued, at least 1 dose of an intravenous bisphosphonate must be given to prevent rebound osteoclast activity that can lead to rapid bone loss and increased risk of fractures.

◊ For patients with creatinine clearance >60 mL/min, we administer zoledronic acid 4 mg over 15 minutes every 4 weeks. If the creatinine clearance is <60 mL/min, we infuse zoledronic acid 4 mg over 30 to 60 minutes every 4 weeks. Acceptable alternatives include pamidronate (90 mg intravenously over 2 hours every 4 weeks) and denosumab (120 mg subcutaneously every 4 weeks).

§ For most patients with moderate kidney impairment, we suggest denosumab rather than a bisphosphonate. Patients with impaired kidney function from myeloma-related causes who normalize kidney function with effective antimyeloma therapy can switch from denosumab to zoledronic acid. Reduced-dose and/or slower infusion rate bisphosphonate is an alternative for those without access to denosumab.