The Accuracy of the International Myeloma Working Group Frailty Score in Capturing Health-Related Quality of Life Profile of Patients with Relapsed Refractory Multiple Myeloma

Abstract

Background Clinical decision-making in patients with relapsed refractory multiple myeloma (RRMM) is challenging and identification of patients who can benefit the most from a given therapy is of critical importance. The International Myeloma Working Group (IMWG) index is one of the most robust scores to evaluate frailty, and it has been validated for patients with newly diagnosed MM. However, little is known on its applicability in the setting of RRMM and of its relationships with patient-reported health-related quality of life (HRQoL). Objectives The primary objective of this study was to investigate whether the IMWG frailty score is able to detect distinct patient-reported HRQoL profiles in the setting of RRMM. A secondary objective was to assess the prevalence of patient-reported clinically important symptoms by frailty groups (ie., fit, intermediate-fit, and frail). Patients and Methods This was an international (Italy and UK) prospective cohort observational study that consecutively enrolled patients from 30 centers. The patients were eligible if they had received at least 1 prior therapy (but no more than 5) and had RRMM according to IMWG criteria. An additional inclusion criterion at the time of study entry was the availability of all variables incorporated into the IMWG frailty score to allow classification of patients in the following three groups: fit, intermediate-fit and frail. Baseline assessment of HRQOL was mandatory to be included in this study and patients completed a set of well-validated measures including the EORTC QLQ-C30 and its myeloma module (QLQ-MY20). The scores from EORTC QLQ-C30 and MY20 questionnaires were summarized by means and standard deviations, overall and by frailty group. Unadjusted differences in mean scores were compared between frailty groups. We also estimated the adjusted mean differences in HRQoL scores of respectively fit and intermediate groups vs frail patients, using a multivariable linear regression model, adjusting for a number of key potential confounders including: sex, education, time since diagnosis, number of previous lines of therapy, previous transplantation, currently receiving therapy, myeloma status (refractory vs relapsed only) and type of MM at diagnosis (secretory vs else). We also assessed the prevalence of clinically important symptoms, based on previously published evidence-based thresholds, by IMWG frailty group. Results Overall, 365 RRMM patients were enrolled between November 2017 and December 2018. Median age was of 69.7 years (IQR, 62.7-75.0) and 296 had received at least two previous lines of therapy. According to the IMWG frailty score evaluation at study entry, 192 (53%), 85 (23%) and 88 (24%) patients were classified as fit, intermediate-fit and frail. Each group was associated with a clearly distinct patient-reported HRQoL profile with both fit and intermediate-fit groups reporting statistically and clinically meaningful better outcomes (ie., improved functional status and lower symptom burden) than frail patients in the majority of the scales from the EORTC QLQ-C30 and QLQ-MY20. For example, mean scores of the EORTC QLQ-C30 physical functioning scale were 71.2, 62.2, and 47.5 for fit, intermediate-fit and frail patients, respectively (p<0.001) (i.e., higher score indicates better functioning). Similarly, the mean score of the QLQ-MY-20 disease symptoms scale was 22.8, 25.9 and 35.9 for fit, intermediate-fit and frail patients, respectively (p<0.001) (i.e., higher score indicates higher symptom burden). Adjusted mean score differences (resulting from multivariable analysis) confirmed clinically relevant differences across most scales of the EORTC QLQ-C30 and QLQ-MY20. Additionally, the prevalence of patient-reported clinically important symptoms was statistically significant different across the three IMWG frailty groups with regard to pain (p=0.002), dyspnea (p=0.004), fatigue (p<0.001), insomnia (p=0.022) constipation (p=0.003) and appetite loss (p=0.001). Details are reported in Figure. Conclusions: In the setting of RRMM, the IMWG frailty score is able to detect clearly distinct patient-reported HRQoL profiles. Current findings may lay the groundwork for the development of a patient-centered frailty index, which also incorporates HRQoL data, to be used in patients with RRMM treated in real-life. Figure 1 Figure 1. Disclosures Efficace: Janssen: Consultancy; Abbvie: Consultancy, Other: Grants (to Institution); Amgen: Consultancy, Other: Grants (to Institution); Takeda: Consultancy. Gaidano: Incyte: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astrazeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Petrucci: BMS: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Karyopharm: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board. Tafuri: Celgene: Research Funding; Roche: Research Funding; Novartis: Research Funding. Larocca: Amgen: Honoraria; Bristol-Myers Squibb: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; GSK: Honoraria; Takeda: Other: Advisory Board. Molica: Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Astrazeneca: Honoraria. Gozzetti: Janssen: Honoraria; AbbVie: Honoraria. Vignetti: Amgen: Consultancy, Honoraria; Incyte: Honoraria; Novartis: Honoraria. Cavo: Novartis: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; Adaptive Biotechnologies: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Measuring Frailty Using Patient-Reported Outcomes (PRO) Data: A Feasibility Study in Patients with Multiple Myeloma

“…We then used PRFP to determine the prevalence of frailty in our study sample. Our findings were in line with a previous prospective cohort study of RRMM patients, albeit one in which the International Myeloma Working Group (IMWG) frailty index was used [28]. Similar to our analysis, 53% of patients in their study were fit, 23% were pre-frail, and 24% were frail [28].…”

“…A key benefit to using patient self-report to measure frailty is that it incorporates the patient’s voice and is a more patient-centric approach [ 28 ]. In their recent study, Efficace et al found a strong correlation between RRMM patients’ frailty status, as measured by the IMWG frailty index, and their self-reported physical functioning and symptom burden as captured by the EORTC QLQ-C30 [ 28 ]. The authors noted that fit , pre-frail , and frail patient groups had distinct patient-reported Health-Related Quality of Life (HRQoL) profiles and concluded that their work paves the way for a patient-centered frailty index [ 28 ].…”

“…Meanwhile, multiple studies in the general non-cancer older adult population have demonstrated the feasibility, reliability, and validity of patient-reported frailty measures [29,30,[54][55][56]. A key benefit to using patient self-report to measure frailty is that it incorporates the patient's voice and is a more patient-centric approach [28]. In their recent study, Efficace et al found a strong correlation between RRMM patients' frailty status, as measured by the IMWG frailty index, and their self-reported physical functioning and symptom burden as captured by the EORTC QLQ-C30 [28].…”

“…Sensitivity analyses were conducted to select the final dichotomization approach. The latter approach was selected due to its congruence with past literature on the prevalence of frailty in MM and its clinical plausibility [ 28 , 38 , 39 ]. Patients were classified as fit if they met none of the five frailty criteria, pre-frail if they met one or two of the frailty criteria, and frail if they met three or more frailty criteria.…”

“…[3]. Alternatively, frailty measures that rely solely on patient self-report shift data capturing to the patient and foster patient-centricity [28][29][30][31]. A resourceful approach to measuring frailty through patient self-report would be to leverage data from routinely administered patient-reported outcome (PRO) assessments.…”