Association of IMWG frailty score with health-related quality of life profile of patients with relapsed refractory multiple myeloma in Italy and the UK: a GIMEMA, multicentre, cross-sectional study

Background The clinical management of patients with relapsed or refractory multiple myeloma is challenging and there is a paucity of tools to help clinicians make more informed decisions for the most suitable treatment options. We aimed to investigate the clinical utility of the International Myeloma Working Group (IMWG) frailty score in the setting of relapsed or refractory multiple myeloma, by examining its ability to capture different patient-reported health-related quality of life profiles. Methods We did a cross-sectional analysis of a prospective observational study of patients with relapsed or refractory multiple myeloma in Italy and the UK (30 hospitals across northern, central, and southern Italy, and one hospital in London, UK). Inclusion criteria were age 18 years or older and patients who had received at least one previous line of therapy and no more than five lines. Participants were excluded if they had a psychiatric disorder or major cognitive dysfunction, or any grade 3 or higher adverse event within 2 weeks before study entry. On study initiation, physicians had to assess frailty according to the IMWG criteria, which included the Charlson Comorbidity Index, the Katz Activity of Daily Living, and the Lawton Instrumental Activities of Daily Living. Patients were asked to complete patient-reported outcome measures, including the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30) and its validated multiple myeloma module (QLQ-MY20). A multivariable linear regression model was used to assess the mean differences in health-related quality of life scores between frailty groups to account for key potential confounding factors. Findings Overall, between Nov 13, 2017, and Nov 15, 2021, 415 patients with relapsed or refractory multiple myeloma, with a median age of 69 center dot 8 years (IQR 62 center dot 8-75 center dot 2) were enrolled. The median time since diagnosis was 4 center dot 4 years (IQR 2 center dot 5-7 center dot 1) and most patients (351 [85%]) had received at least two previous lines of therapy. According to the IMWG frailty score, 200 (48%) were classified as fit, 112 (27%) were classified as intermediate-fit, and 103 (25%) patients were classified as frail. Each frailty group was associated with a distinct health-related quality of life profile, with most notable differences between fit and frail patients. The largest clinically meaningful adjusted differences between fit and frail patients by the EORTC QLQ-C30 questionnaire were observed for physical functioning (Delta=-19 center dot 0 [95% CI -25 center dot 6 to -12 center dot 5; p<0 center dot 0001), fatigue (Delta=16 center dot 7 [9 center dot 7 to 23 center dot 7]; p<0 center dot 0001), insomnia (Delta=13 center dot 4 [4 center dot 1 to 22 center dot 6]; p=0 center dot 0047), and dyspnoea (Delta=12 center dot 5 [4 center dot 6 to 20 center dot 4]; p=0 center dot 0021). The most prevalent clinically important symptom in the overall population was pain; however, its prevalence varied between IMWG frailty groups at 70 center dot 9% in frail patients, 55 center dot 9% in intermediate-fit patients, and 50 center dot 5% in fit patients. Interpretation Our findings show the clinical utility of the IMWG frailty score in the setting of relapsed or refractory multiple myeloma, in helping to distinguish between groups of patients with distinct health-related quality of life profiles. Further research is needed to examine the value of patient-reported outcome data in improving assessment of frailty in the setting of relapsed or refractory multiple myeloma.