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Frailty index predicts outcomes for older patients with myeloma
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A deficit-accumulation frailty index that accounts for aging-associated diseases and disabilities appeared prognostic of OS among older patients with myeloma, according to study findings.
Patients considered frail using the index had a 63% higher risk for mortality than patients deemed nonfrail. Thus, the index can help inform decision-making for older patients by incorporating functional and quality-of-life factors rather than chronological age alone.
“Personalized medicine should be tailored not just for disease-specific factors or the latest genomic tests, but also patient-specific factors. ... Patients rely on the data we give them as they consider their treatment options, preferences and goals of care,” study author Tanya S. Wildes, MD, MSCI, of Washington University School of Medicine in St. Louis, told HemOnc Today. “We need to be able to provide them with information regarding the impact of both their cancer and their overall fitness/frailty on their expected course.”
It has remained a challenge to differentiate between patients with myeloma who can tolerate aggressive treatments with feebler patients at risk for morbidities and mortality from toxicities.
Tools such as a frailty index and Myeloma Comorbidity Index have been developed to risk stratify older patients with myeloma; however, biologic age or functional age — for which an individual’s health status is quantified as a proportion of their age-associated deficits — are not taken into consideration.
Previous research showed a frailty index based on deficit-accumulation principle — the use of information from various variables of an individual’s health — can define age-related decline in health better than chronological age.
“There are many approaches to measuring frailty, and even international experts in frailty have not come to a consensus on exactly how to define or measure it,” Wildes said.
Wildes and colleagues used the deficit-accumulate principle to develop a deficit-accumulation frailty index based on data from 2,692,361 individuals without cancer (median age, 74 years) — the derivation cohort — from the Medicare Health Outcomes Survey (MHOS) and SEER-MHOS linked database.
From 132 potential variables, investigators selected 25 variables to create the deficit-accumulation frailty index. Variables mentioned in the deficit-accumulation frailty index included difficulty eating, bathing, hearing, walking and limitations in activities.
“Rather than looking at individual factors that would be expected to impact prognosis (e.g. comorbidities or performance status), the accumulation of deficits approach incorporates a range of aging-related issues, some of which may not be independently prognostic (like hearing impairment),” Wildes said. “Rather, when taken as a whole, the index represents the cumulative burden of vulnerabilities.”
Individuals in the derivation cohort had a mean frailty index of 0.23 (standard deviation [SD], 0.17). Among this cohort, researchers found each 10% increase in frailty index to be associated with 40% increased risk for mortality (adjusted HR = 1.39; 95% CI, 1.39-1.39).
Researchers then applied the frailty index to 305 patients with newly diagnosed myeloma aged 65 years and older (median age, 76 years) identified in the SEER-MHOS database. These patients had a mean frailty index of 0.28 (SD, 0.17).
Investigators found each 10% increase in frailty index to be associated with 16% increased risk for mortality among patients with myeloma (adjusted HR = 1.15; 95% CI, 1.08-1.24).
Fifty-three percent of patients were considered frail according to the index.
Median OS was 43.7 months among patients not considered frail compared with 26.8 months among frail patients (P = .015).
Multivariable analysis showed frail status was associated with a 63% increased risk for death (adjusted HR = 1.63; 95% CI, 1.33-2.22). Frailty status remained significantly associated with OS even after controlling for chronological age. Male sex appeared associated with decreased OS, which is consistent with previous studies, the researchers wrote.
Wildes cited a lack of data on myeloma-specific factors, including Revised-International Staging System stage, and scarcity of data on myeloma treatments in the SEER-MHOS dataset, as study limitations.
“This precludes conducting survival analyses that also control for disease-specific factors and prevents us from understanding the impact of treatment selection on survival,” Wildes said.
It will be important to acknowledge the reaction of an individual patient’s health and vulnerability on outcomes and understanding age-specific burdens, according to Wildes.
“Whether using this SEER-MHOS Frailty Index, or other approaches that have been used in myeloma — including the International Myeloma Working Group Frailty Model or the Revised Myeloma Comorbidity Index — I would love to see the baseline characteristics table of manuscripts include data that would help us understand the prevalence of aging-associated vulnerabilities in the population studied,” Wildes said. “This will help me understand whether the data I am looking at apply to the patient sitting in front of me.” – by Melinda Stevens
For more information:
Tanya S. Wildes, MD, MSCI , can be reached at Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110; email: twildes@wustl.edu.
Disclosures: Wildes reports honoraria from Carevive Systems and research funding to her institution from Janssen Oncology. Please see the study for all other authors’ relevant financial disclosures.
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