Bisphosphonates should be prescribed for any patient receiving treatment for active multiple myeloma, regardless of whether or not there is evidence of lytic bone destruction or spinal compression fracture, according to updated guidelines from the American Society of Clinical Oncology.
Previous guidelines from the society, last updated in 2007, recommended the use of intravenous bisphosphonates for patients with myeloma with evidence of bone disease, according to the expert panel that drafted the update.
Dr. Kenneth C. Anderson
“Fewer adverse events related to renal toxicity have been noted with denosumab, compared with zoledronic acid,” and “this may be preferred in patients with compromised renal function,” wrote the expert panel, led by cochairs Kenneth C. Anderson, MD, of Dana-Farber Cancer Institute, Boston, and Robert A. Kyle, MD, of Mayo Clinic, Rochester, Minn.
ASCO guidelines on bisphosphonates in myeloma were first drafted in 2002 and then updated in 2007. The new recommendations on bone-modifying therapy in myeloma are based on review of an additional 35 publications. The new guidelines are “consistent with the previous recommendations” while updating indications for therapy and information on denosumab, according to the expert panel.
Evidence that myeloma patients without lytic bone disease will benefit from intravenous bisphosphonates comes from the randomized MRC IX trial, in which patients who received zoledronic acid had reduced skeletal-related events at relapse and improved progression-free survival.
Denosumab, a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor, was noninferior to zoledronic acid for prevention of skeletal-related events in a randomized phase 3 clinical trial; however, it is “more expensive than zoledronic acid or pamidronate and must be considered in treatment decisions,” the guidelines authors wrote.
The total price in the United States for a 1-year treatment cycle of denosumab is just under $26,000, according to data included in the ASCO guideline. By comparison, the 1-year treatment cycle price for the bisphosphonates ranges from $214 to $697, depending on the regimen.
When intravenous bisphosphonate therapy is warranted, the guideline-recommended schedule is infusion of zoledronic acid 4 mg over at least 15 minutes, or pamidronate 90 mg over 2 hours, every 3-4 weeks.
The guidelines also address osteonecrosis of the jaw (ONJ), a major complication observed not only with the potent bisphosphonates pamidronate and zoledronic acid, but also with denosumab.
The panel said they were in agreement with revised labels from the Food and Drug Administration for zoledronic acid and pamidronate, among other papers or statements addressing ONJ and noted that patients need a comprehensive dental exam and preventive dentistry as appropriate before starting bone-modifying therapy.
“The risk of ONJ has prompted the use of less-frequent dosing of zoledronic acid, which may be an option for patients,” they said in their report.
Guideline authors reported ties to Amgen, Celgene, Millennium Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, Novartis, Pfizer, and others.
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SOURCE: Anderson K et al. J Clin Oncol. 2018 Jan 17:JCO2017766402. doi: 10.1200/JCO.2017.76.6402.