Purpose To update guideline recommendations on the role of bone-modifying agents in
multiple myeloma. Methods An update panel conducted a targeted systematic literature review by searching PubMed and the Cochrane Library for randomized controlled trials, systematic reviews, meta-analyses, clinical practice guidelines, and observational studies. Results Thirty-five relevant studies were identified, and updated evidence supports the current recommendations. Recommendations For patients with active symptomatic
multiple myeloma that requires systemic
therapy with or without evidence of lytic destruction of bone or
compression fracture of the spine from
osteopenia on plain radiograph(s) or other imaging studies,
intravenous administration of
pamidronate 90 mg over at least 2 hours or
zoledronic acid 4 mg over at least 15 minutes every 3 to 4 weeks is recommended.
Denosumab has shown to be noninferior to
zoledronic acid for the prevention of skeletal-related events and provides an alternative. Fewer adverse events related to renal toxicity have been noted with
denosumab compared with
zoledronic acid and may be preferred in this setting. The update panel recommends that clinicians consider reducing the initial
pamidronate dose in patients with preexisting renal impairment.
Zoledronic acid has not been studied in patients with severe renal impairment and is not recommended in this setting. The update panel suggests that bone-modifying treatment continue for up to 2 years. Less frequent dosing has been evaluated and should be considered in patients with responsive or stable disease. Continuous use is at the discretion of the treating physician and the risk of ongoing skeletal morbidity.
Retreatment should be initiated at the time of disease relapse. The update panel discusses measures regarding
osteonecrosis of the jaw. Additional information is available at www.asco.org/
hematologic-malignancies-guidelines and www.asco.org/guidelineswiki .