Health-Related Quality of Life as Assessed by the EQ-5D-5L Predicts Outcomes of Patients Treated with Azacitidine—A Prospective Cohort Study by the AGMT

SIMPLE SUMMARY: The EuroQol 5-Dimension 5-level (EQ-5D-5L) questionnaire is a globally used and multiply validated tool to assess health-related quality of life (HRQoL), but data on its use for patients with myeloid neoplasias is scarce. The aim of this prospective cohort study was to alleviate this knowledge gap. Our data show in a homogenous population of azacitidine-treated patients for the first time that (1) myeloid patients have significantly worse HRQoL than a population norm (i.e., a representative sample of the German general adult population) from a similar geographic region, matched by age, sex and number of comorbidities; (2) The EQ-5D-5L questionnaire response provides added prognostic value to the International Prognostic Scoring System (IPSS) and the revised IPSS (R-IPSS), which are longstanding gold standards of prognostication in these diseases; (3) the multivariate-adjusted significant predictive value of the EQ-5D-5L response parameters on patient outcomes including response to azacitidine, time to next treatment and overall survival; (4) longitudinal assessment of the EQ-5D-5L response/clinical parameter pairs revealed significant additional, independent associations. ABSTRACT: In this prospective study (NCT01595295), 272 patients treated with azacitidine completed 1456 EuroQol 5-Dimension (EQ-5D) questionnaires. Linear mixed-effect modelling was used to incorporate longitudinal data. When compared with a matched reference population, myeloid patients reported more pronounced restrictions in usual activities (+28%, p < 0.0001), anxiety/depression (+21%, p < 0.0001), selfcare (+18%, p < 0.0001) and mobility (+15%, p < 0.0001), as well as lower mean EQ-5D-5L indices (0.81 vs. 0.88, p < 0.0001), and lower self-rated health on the EuroQol Visual Analogue Scale (EQ-VAS) (64 vs. 72%, p < 0.0001). After multivariate-adjustment, (i) the EQ-5D-5L index assessed at azacitidine start the predicted time with clinical benefit (TCB) (9.6 vs. 6.6 months; p = 0.0258; HR = 1.43), time to next treatment (TTNT) (12.8 vs. 9.8 months; p = 0.0332; HR = 1.42) and overall survival (OS) (17.9 vs. 12.9 months; p = 0.0143; HR = 1.52); (ii) Level Sum Score (LSS) predicted azacitidine response (p = 0.0160; OR = 0.451) and the EQ-5D-5L index showed a trend (p = 0.0627; OR = 0.522); (iii) up to 1432 longitudinally assessed EQ-5D-5L response/clinical parameter pairs revealed significant associations of EQ-5D-5L response parameters with haemoglobin level, transfusion dependence and hematologic improvement. Significant increases of the likelihood ratios were observed after addition of LSS, EQ-VAS or EQ-5D-5L-index to the International Prognostic Scoring System (IPSS) or the revised IPSS (R-IPSS), indicating that they provide added value to these scores.