Boston—Most patients with hematologic malignancies are older, and many have multiple chronic conditions in addition to blood cancer. Polypharmacy has an even greater risk of adverse effects for these patients because of cancer treatment and medications used to manage side effects.

A recent study in the Journal of the National Comprehensive Cancer Network pointed out that most older blood cancer patients take five or more medications.

The researchers and colleagues from Brigham and Women's Hospital and the Dana-Farber Cancer Institute examined how polypharmacy in older patients with blood cancer affects their risk of frailty.

The study team created a new scale based on a list of Potentially Inappropriate Medications (PIMs), the Geriatric Oncology-Potentially Inappropriate Medications (GO-PIMs) Scale and determined it to be more effective at predicting frailty than other methods.

"A large portion of research for older adults identifies patients as 'having polypharmacy' (i.e., taking multiple medications at the same time, leading to a higher risk of adverse events) based on a cutoff of five or more medications; but they don't specify which medications. Unfortunately, 50% of Americans 75-and-older meet this definition for polypharmacy, making it challenging for busy oncology teams to adequately review chronic medications in order to prevent potential problems," explained co-lead author Tammy T. Hshieh, MD, MPH, of Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School.

"We were interested in the NCCN list of medications of concern because, in contrast to other lists, it was developed by geriatricians and oncologists to be specific for older adults with cancer. We found the GO-PIMs scale we created based on this list carried the strongest association with frailty and can be used by oncology teams to help decrease inappropriate medication usage in an effective way to potentially improve patients' overall health," Dr. Hshieh added.

"The health risks from these specifically identified medications—including falls and fatigue—often outweigh their benefits, especially in older adults whose ability to tolerate side effects are reduced," added co-lead author Clark DuMontier, MD, MPH, also with Brigham and Women's Hospital and Harvard Medical School. "Our GO-PIMs tool makes it easier for oncology teams to identify these medications and consider deprescribing them. This scale can also be easily converted into an automated tool that identifies high-risk medications within an electronic health record."

The background information in the articles noted that certain prescription drugs, called PIMs, are associated with adverse effects in older patients. "These medications are potentially inappropriate because there are alternatives with safer adverse effect profiles. Examples include corticosteroids (oral), sedatives, antihistamines, opioids, and antipsychotics. In the general older population, polypharmacy and PIMs have been found to be a risk factor for the development and progression of frailty," the researchers explained.

The report pointed out that older patients with cancer "are also undoubtedly affected," adding that the NCCN Clinical Practice Guidelines for Older Adult Oncology include a list of medications commonly used for supportive care but might be problematic for older adults.

"This list has the potential to be a cancer-specific PIMs scale, but the association of the listed medications with adverse outcomes in patients with cancer has yet to be demonstrated," the authors add.

They pointed out that functional decline, cognitive impairment, and frailty are all prevalent in older adults with blood cancers. The concern is that polypharmacy and PIMs are likely to exacerbate the geriatric syndromes, especially when combined with toxicity and other adverse outcomes during cancer treatment.

"On the other hand, there are sparse data regarding the best ways to identify PIMs for older adults with blood cancers, and whether polypharmacy and PIMs are associated with frailty in this population," the study stated. "Frailty is a state of reduced physiologic reserve that leaves one vulnerable to future stressors, and evidence in other populations of older adults suggests that polypharmacy is strongly linked to frailty, identifying it as a potentially modifiable risk factor."

In response, researchers examined the prevalence of polypharmacy and PIMs in a large cohort of patients with blood cancers. They also analyzed the association with frailty and cognitive decline with several polypharmacy and PIM definitions. Their hypothesis was that polypharmacy and PIMs would be involved and associated with increasing frailty, although the presence of PIMs would be more predictive.

"We based our hypothesis on the supposition that an increase in the total number of medications—and dichotomizing above or below a certain cutoff—does not confer as strong a risk of frailty as does an increase in the number of inappropriately prescribed medications, the latter of which also points to deprescribing interventions," the authors wrote.

The study team focused on 785 transplant-ineligible blood cancer patients aged 75 years and older treated at Dana-Farber Cancer Institute between February 2015 and November 2019. The results indicated that each additional "unspecified" medication in general increased the relative odds of being prefrail or frail by 8%, while each additional medication on the GO-PIMs scale increased the relative odds by 65%.

The researchers reported that—compared with robust patients—frail and prefrail patients were more likely to be taking benzodiazepines, selective serotonin reuptake inhibitors, or corticosteroids.

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