The use of a frailty scale constructed from existing patient-reported outcomes (PRO) items routinely collected in clinical trials is a feasible approach for measuring frailty in patients with multiple myeloma (MM), according to research published in Quality of Life Research.

“Interest in frailty-directed treatment optimization has been growing in oncology due to its potential for minimizing toxicity, improving tolerability, and lengthening duration of treatment to potentially improve survival,” the researchers explained in their report.

The team conducted an exploratory retrospective study to determine the feasibility of measuring frailty using patient responses to select items of the European Organization for Research and Treatment of Cancer Quality of Life 30-item Questionnaire (EORTC QLQ-C30) as proxy criteria for the Fried Frailty Phenotype in patients with relapsed or refractory (RR) MM.

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The researchers pooled data from 9 phase 3 randomized clinical trials for the treatment of RRMM that were submitted to the US Food and Drug Administration for regulatory review between 2010 and 2021. They then constructed a patient-reported frailty phenotype (PRFP) based on the Fried definition of frailty using baseline EORTC QLQ-C30 responses collected during the trials. The PRFP was evaluated for internal consistency reliability, structural validity, and known groups validity.

The 5 candidate EORTC QLQ-C30 items for the PRFP included: Have you lacked appetite? (proxy for unintentional weight loss); Did you need to rest? (proxy for exhaustion, typically self-reported); Have you felt weak? (proxy for weakness, typically measured by grip strength); Do you have any trouble taking a short walk outside of the house? (proxy for slowness, typically measured by observing gait speed); and Were you limited in doing either your work or other daily activities? (proxy for low physical activity, typically measured using the short version of the Minnesota Leisure Time Activity Questionnaire). Some alternate candidate items were also considered.

The study demonstrated the selected items were good indicators of frailty, with factor loadings (an indicator of the strength of the relationship between an item and the underlying construct) ranging from 0.66 to 0.88 and R2 values ranged from 0.43 to 0.77. The items were also well correlated with one another, with r ranging from 0.48 to 0.74.

The PRFP showed adequate internal consistency reliability (Cronbach’s α, 0.85; 95% CI, 0.84-0.85) and structural validity assessed by confirmatory factor analysis (scaled χ2 [df] = 171.83 [5]; P ≤.05; root mean square error of approximation, 0.082; 95% CI, 0.072-0.093; comparative fit index, 0.99; standardized root mean square residual, 0.03; Tucker Lewis Index, 0.99).

Of the 4928 patients (mean age, 65 years; range, 30–91; age >65 years, 46.8%) included in the study, 55.4% were classified as fit, 24.5% as pre-frail, and 20.1% as frail according to the PRFP.

The study also demonstrated that PRFP could be used to detect distinct comorbidity levels and distinguish between different functional profiles. For example, patients with frailty reported more difficulty with mobility (88% of frail vs 69% of pre-frail vs 31% of fit; P <.05), self-care (54% of frail vs 28% of pre-frail vs 7% of fit; P <.05), and performing their usual activities (93% of frail vs 76% of pre-frail vs 33% of fit patients; P <.05) than patients considered pre-frail and fit.

“Given the significance of frailty at the individual and population levels, having a simple yet effective tool that can be easily deployed in diverse settings ranging from clinical practice to decentralized trials could be valuable,” the researchers noted. “Our initial exploration of clinical trial data in MM patients suggests that it is feasible to leverage patients’ responses to selected items of the EORTC QLQ-C30 to measure frailty.”

Limitations of the study included the construction of the example PRFP for the study as only a proof of concept, discussion and selection of candidate EORTC QLQ-C30 items corresponding to each Fried frailty criterion only amongst the study authors, not including patients and subject matter experts, assessment of the selected EORTC

QLQ-C30 intermittently not sequentially, differences in recall windows amongst the items, and unknown concordance between PRFP and other widely accepted frailty measures in MM.


Murugappan MN, King-Kallimanis BL, Bhatnagar V, et al. Measuring frailty using patient-reported outcomes (PRO) data: a feasibility study in patients with multiple myeloma. Qual Life Res. Published online March 20, 2023. doi:10.1007/s11136-023-03390-5