Different IV Bisphosphonates Dosing Tied to Similar Skeletal Event Rates in Multiple Myeloma

Lisa Rapaport

August 02, 2021

(Reuters Health) — The risk of recurrent skeletal-related events in patients with multiple myeloma is similar with intravenous (IV) bisphosphonate dosing schedules ranging from 4 weeks to longer than 12 weeks, a new study suggests.

Researchers examined data on 4,281 adults newly diagnosed with multiple myeloma in the IBM MarketScan Databases between January 1, 2009, and September 30, 2015. All patients received IV bisphosphonates; the primary study goal was to determine the risk of recurrent skeletal-related events associated with either the recommended 4-week dosing interval or extended dosing intervals of 5-8 weeks, 9-12 weeks, or longer than 12 weeks.

After a median follow up from diagnosis of 13.3 months, 2,567 (60%) patients experienced at least one skeletal-related event, which researchers defined as hypercalcemia, spinal cord compression, pathological fracture, or other conditions requiring surgery or radiotherapy to the affected bone.

Compared to dosing IV bisphosphonates every 4 weeks, there was no statistically significant difference in risk of skeletal-related events with dosing 5-8 weeks (hazard ratio, 1.00), 9-12 weeks (HR, 0.95), or longer than 12 weeks (HR, 0.90), researchers report in JAMA Network Open.

"This real-world study, as well as clinical trials of mostly breast and prostate cancer patients, indicates that IV bisphosphonates can be given safely at intervals less frequent than every 4 weeks, including up to every 12 weeks, without a significant increase in risk of a skeletal related event," said senior study author Gregory Calip, an associate professor in the College of Pharmacy at the University of Illinois at Chicago.

While the optimal dosing frequency for bisphosphonates to treat cancer-related bone disease is not known, more frequent clinic visits for infusions can be a burden to cancer patients, Calip said by email.

"Amid concerns for patient safety, such as the increased risks of severe COVID-19 related illness among patients with hematologic malignancies, understanding when and for how long supportive cancer treatments like bisphosphonates can be delayed is critical for clinical decision making," Calip added.

One limitation of the observational study design is the potential for misclassification or unmeasured confounding to influence the results, the authors note.

The study also wasn't designed to identify the superiority of one dosing frequency over another, said Dr. Shiva Kumar Reddy Mukkamalla, an attending physician in hematology and medical oncology at Presbyterian Medical Group in Rio Rancho, New Mexico, who wasn't involved in the study.

It's possible that after the first dose of IV bisphosphonates, there is a significant change in bone turnover rate, which could be measured by serum or urinary terminal telopeptide levels, and the frequency of subsequent IV bisphosphonates doesn't have as much impact on skeletal-related events, Dr. Mukkamalla said by email.

"Skeletal-related events are very frequent in myeloma patients and require preventive efforts," said Dr. Dr. Clifford Rosen, a professor at Tufts University School of Medicine in Boston and a senior scientist at Maine Medical Center Research Institute in Scarborough.

"Bisphosphonates are an important adjunct in the management of these patients and the frequency of administration may be longer than anticipated," Dr. Rosen, who wasn't involved in the study, said by email. "Conceivably bisphosphonates could be administered in a frequency as long as every 3 months."

SOURCE: https://bit.ly/2VmieC2 JAMA Network Open, online July 27, 2021.

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