Pretreatment Health-Related Quality of Life Profile According to the EORTC QLQ-C30 in Patients with Myelodysplastic Syndromes (MDS): Analysis on 443 Lower-Risk MDS Patients
Authors: Efficace Fabio , Niscola Pasquale , Patriarca Andrea , Cottone Francesco , Palumbo Giuseppe A. , Caocci Giovanni , Fedele Marilena , Platzbecker Uwe , Stauder Reinhard , Petranovic Duska , Ricco Alessandra , Breccia Massimo , Frairia Chiara , Luppi Mario , Invernizzi Rosangela , Sanpaolo Grazia , Crugnola Monica , Fianchi Luana , Vallisa Daniele , Voso Maria Teresa , Fozza Claudio , Santini Valeria , Caers Jo , Capodanno Isabella , Sarlo Chiara , Pelaez Doro Maribel , Bergamaschi Micaela , Zhang Huiyong , Lubbert Michael , Canicattì Manuela , Kyriakou Charalampia , Di Renzo Nicola , Cuneo Antonio , Karakantza Marina , Vignetti Marco 
Published: October 2019

Abstract
Background:
Understanding health-related quality of life (HRQOL) profile, including functional aspects and symptom burden, of yet untreated patients with myelodysplastic syndromes (MDS) is important to help clinicians to better identify subgroup of patients in need of special attention from the very beginning of therapy.
Aims:
The primary objective of this study was to investigate baseline (i.e., pretreatment) HRQOL profile of untreated patients with lower-risk MDS, examining differences by age, gender, risk score category and comorbidity. A secondary objective was to provide age and sex baseline reference HRQOL values, according to the EORTC QLQ-C30 questionnaire, to be used as benchmark comparisons in future MDS studies.
Methods:
This analysis is based on 443 newly diagnosed adult MDS patients with International Prognostic Scoring System (IPSS) risk score of low (46 %) or intermediate-1 (54%), enrolled in an international prospective cohort observational study. Median age was 75 years (range 32-94), with 261 men (59%) and 182 (41%) women. HRQOL was assessed by the EORTC QLQ-C30 questionnaire at study entry, before any treatment (except for transfusions). This well validated questionnaire consists of five functioning scales: physical, role, emotional, cognitive and social; three symptom scales: fatigue, nausea/ vomiting and pain; six single item scales: dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact; and the global health status/HRQOL scale. The items were scaled and scored using the recommended EORTC procedures. At the time of baseline HRQOL assessment, 111 (25%) patients had received at least one red blood cell transfusion. We used Wilcoxon-Mann-Whitney and Kruskal-Wallis tests for all comparisons. We used the false discovery rate approach to account for multiple testing, with a nominal α-level=0.05. In addition to statistical significance, clinically relevant HRQOL differences were also evaluated based on previously published criteria (Cocks K, et al, J Clin Oncol 29:89-96, 2011).
Results:
There were not statistically significant differences in any of the HRQOL scales measured by the EORTC QLQ-C30, by the specific IPSS risk category (i.e., low risk vs intermediate-1 risk score). Overall, women reported worse HRQOL scores than men, with clinically relevant differences for physical (Δ=-7.1, P=0.002), role (Δ=-9.9, P=0.002) and emotional functioning, (Δ=-10, P<0.001), nausea/vomiting (Δ=3.7, P<0.001), insomnia (Δ=7.6, P=0.011) and appetite loss (Δ=5.6, P=0.019). Younger patients also reported better outcomes than older patients and this was more evident in the Physical Functioning domain. Also, HRQOL profile varied substantially by number of comorbidities (zero, one, two or more). In general, there was a worsening HRQOL trend with the increase of comorbidities. However, HRQOL impairments were markedly larger in patients with at least two comorbidities, who showed both small and medium clinically relevant differences, when compared to patients with no comorbidities. The largest differences between patients with no comorbidity and those with two or more were found in the following HRQOL domains: Physical Functioning (Δ=-15.3, P<0.001), Fatigue (Δ=-11.9, P<0.001) and Global health status/QOL (Δ=10.0, P<0.001). Full baseline reference values by specific age group categories and sex, according to the EORTC QLQ-C30, are reported in Table 1.
Conclusion:
Pretreatment HRQOL profile in lower-risk MDS patients vary substantially by age group categories, sex and number of comorbidities, and these differences should be highly considered at the time of treatment start. As in MDS research, the EORTC QLQ-C30 is currently one of the most frequently used HRQOL measure, our baseline reference values provide benchmark data against which other MDS studies using this questionnaire may be compared.

Disclosures
Efficace: Bristol Meyers Squibb: Consultancy; Seattle Genetics: Consultancy; Orsenix: Consultancy; Incyte: Consultancy; TEVA: Research Funding; TEVA: Consultancy; Lundbeck: Research Funding; Amgen: Consultancy; AMGEN: Research Funding. Palumbo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Platzbecker:Celgene: Research Funding. Stauder:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Breccia:Novartis: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Voso:Celgene: Research Funding, Speakers Bureau. Santini:AbbVie: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy; Novartis: Honoraria. Lubbert:Teva: Other: Study drug; Celgene: Other: Travel Grant; Janssen: Honoraria, Research Funding. Cuneo:Gilead: Other: advisory board, Speakers Bureau; Abbvie: Other: advisory board, Speakers Bureau; Roche: Other: advisory board, Speakers Bureau; janssen: Other: advisory board, Speakers Bureau.