Bortezomib Appears to Increase Fall Risk in Elderly Patients With MM, Study Suggests

First-line bortezomib (Velcade) appears to be linked with a heightened risk of falls in elderly patients with multiple myeloma (MM), according to new research.

The study, published in the Journal of Geriatric Oncology, also suggested that patients who experience a fall within the first year on bortezomib face a higher risk of mortality. The investigators cautioned that further research is needed to confirm the findings.

Corresponding author Kelly L. Schoenbeck, MD, of the University of California San Francisco, and colleagues, explained that older patients have a higher risk of falls in general, and older adults with cancer have been shown to have a higher risk of falling than matched controls without cancer. The reasons for that risk include functional and cognitive impairment, depression, high-risk medications, frailty, and other factors.

MM primarily impacts older adults, with a median age of 70 at diagnosis. It is often treated with the proteasome inhibitor bortezomib, a drug that has been linked with peripheral neuropathy. Schoenbeck and colleagues therefore hypothesized that patients taking the drug might face a higher risk of falls; however, that premise had not yet been tested in a scientific analysis.

Schoenbeck and colleagues decided to consult the Surveillance, Epidemiology, and End Results (SEER) Program-Medicare database to identify patients 65 years old and older who were diagnosed with MM between 2007 and 2013 and were enrolled in Medicare parts A, B, or D. All patients who met inclusion criteria and began therapy for MM within 6 months of diagnosis were included, and their records were analyzed through 2014 to find claims related to cancer treatment, falls, and certain covariates.

The investigators identified 4084 older adults who were diagnosed with MM and met inclusion criteria. Of those, 271 (6%) had fall-related claims in the year prior to initiation of treatment, and a similar number, 259 (6%), had falls in the first 12 months after treatment (the median time to fall was 129 days). Only a small minority of patients with a fall (8%) had falls in both the pre- and post-treatment-initiation periods.

Of the more than 4000 patients included in the study, half (2052 patients) received bortezomib as first-line therapy. Of those, 157 (8%) experienced a fall within 12 months of treatment, compared to just 192 (5%) patients who did not receive bortezomib.

The investigators also found that diagnostic codes for peripheral neuropathy were more common in the bortezomib group (27.7% versus 14.8%), and those with peripheral neuropathy were more likely to experience falls, the data showed.

A multivariate analysis translated the findings into a 36% increased risk for falls among the patients receiving bortezomib. Further analysis revealed that, among patients who survived at least 12 months after initiation of treatment, the median overall survival of patients who experienced a fall was 35.7 months, compared to 49.1% for those patients who did not experience a fall. Thus, a first-year fall was associated with a 26% increased risk of death.

“We hypothesize the mechanism between bortezomib and falls among patients with multiple myeloma is treatment-related neuropathy,” Schoenbeck and colleagues wrote. “In support of this, we found that bortezomib, peripheral neuropathy, and falls are all associated.”

However, the authors also cautioned that it was not possible to conclusively draw a causal connection, in part because codes for symptoms like peripheral neuropathy may present themselves considerably earlier than they appear in Medicare claims, making it difficult to know the actual temporal relationship between the symptoms and the fall.

The investigators said further study is important, in part because if bortezomib increases the risk of falls, those falls appear to increase the risk of death.

“Given the preventable nature of falls, it will be imperative that future research focus on prospective fall-risk assessments and interventions that can mitigate fall risks in this patient population,” they concluded.

Reference

Schoenbeck KL, Fiala MA, Wildes TM. Bortezomib in first-line therapy is associated with falls in older adults with multiple myeloma [published online ahead of print, 2021 Mar 6]. J Geriatr Oncol. 2021;S1879-4068(21)00018-7. doi:10.1016/j.jgo.2021.02.009