By Ed Susman, Contributing Writer, MedPage Today

Published: June 06, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

CHICAGO – Osteonecrosis of the jaw remains a relatively rare event among multiple myeloma patients treated long-term with bisphosphonate therapy, researchers said here.

"Overall cumulative osteonecrosis of the jaw was low at 5.8 years," Gareth Morgan, MD, PhD, of the Institute of Cancer Research at the Royal Marsden Hospital in London, said in an oral presentation at the annual meeting of the American Society of Clinical Oncology.

The rate was 3.7% in the patients on zoledronic acid (Zometa) and 0.5% (P<0.001) with clodronate, with most events occurring in the 12-to-36-month time window, Morgan said. However, he noted that if patients were also receiving thalidomide therapy to battle myeloma, the overall rate of osteonecrosis of the jaw dropped to around 1% of the patients.

He discussed updates to the MRC Myeloma IX study, in which 1,960 patients were assigned to different treatment strategies that included stratification by type of bisphosphonate assigned.

In the overall study that has been previously reported, treatment with zoledronic acid was associated with an overall survival benefit (P=0.03), overall increased progression-free survival (P=0.01), and a reduction in skeletal events.

This year, Morgan focused on how treatment affected adverse events including renal disease and osteonecrosis of the jaw. Renal disease emerged in about 5% to 7% of patients on either zoledronic acid or clodronate, in either treatment strategy over the long-term study, he said. At 2 years, cumulative renal failure events occurred in 5.2% of patients on zoledronic acid and in 5.8% of patients on clodronate.

"Renal impairment is common in patients with multiple myeloma," Morgan said in his oral presentation. He said renal disease can be caused by myeloma itself as well as patients' susceptibility to infection. Anti-myeloma therapy and anti-resorptive therapy with bisphosphonates also may increase kidney risks.

Similarly, Morgan said, osteonecrosis of the jaw has emerged as a disease/treatment adverse event troubling to doctors and their patients. He defined osteonecrosis of the jaw as exposed bones in the maxillofacial area that occur in association with dental surgery, or occur spontaneously, with no evidence of healing.

Morgan also noted that among patients for whom recovery data was available, four of nine patients on zoledronic acid who developed osteonecrosis of the jaw made a complete recovery, and two others showed improvement. No change was observed in the other patients.

"The message of that trial is to show that osteonecrosis of the jaw is a relatively rare event," said Rafael Fonseca, MD, professor of medicine at the Mayo Clinic in Scottsdale, Ariz. "The important message of the trial is to show that a more powerful bisphosphonate does help with bone disease. It showed that overall survival was better with zoledronic acid."

Morgan said that to prevent osteonecrosis of the jaw, all patients should receive a comprehensive dental examination before treatment with bisphosphonates, including the removal of unsalvageable teeth. All invasive dental procedures should be completed before initiating bisphosphonate therapy, periodontal procedures should be completed, and ill-fitting dentures should be fixed prior to treatment.

Fonseca disclosed commercial interests with Amgen, Bristol-Myers Squibb, Celgene, Genzyme, Medtronic, Otsuka, Cylene, and Proteloix.

Morgan disclosed commercial interests with Celgene, Johnson & Johnson, Merck, and Novartis. Other researchers disclosed commercial interests with Celgene, Janssen-Cilag, Novartis, Ortho Biotech, and Abbott Laboratories.

Primary source:American Society of Clinical Oncology
Source reference:
Morgan G, et al "Efficacy and side-effect profile of long-term bisphosphonate therapy in patients with multiple myeloma: MRC myeloma IX study results" J Clin Oncol 2012; (suppl)30; Abstract 8015.

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