BACKGROUND: In our previous study on erythropoiesis-stimulating agent (ESA) treatment in lower risk myelodysplastic syndromes from the European MDS (EUMDS) Registry, we showed that patients treated with ESAs had longer survival compared with patients who receive red blood cell transfusion (RBCT). In this study, with a longer follow up time and more patients included, we aimed to assess long-term effects on survival and health-related quality of life (HRQoL) of exposure to ESAs with or without RBCT in patients with lower risk myelodysplastic syndromes. METHODS: The EUMDS Registry is a non-interventional, longitudinal, real-world registry prospectively enrolling newly diagnosed patients older than 18 years with lower risk (International Prognostic Scoring System low or intermediate-1) myelodysplastic syndromes from 16 European countries and Israel. The analysis was restricted to patients with haemoglobin concentrations less than 100 g/L enrolled between Jan 1, 2008, and July 1, 2019, with last censoring of data on Dec 31, 2021. Patient management was recorded every 6 months, including treatment, transfusions, and HRQoL. ESA treatment followed local guidelines. The patients were separated into four groups at each study visit: no ESA or RBCT, ESA only, ESA plus RBCT, and RBCT only. The data were analysed longitudinally over time according to ESA and RBCT status during each 6-month interval, using propensity score matching. The main outcomes were median overall survival and leukaemia-free survival, and HRQoL. This study is registered with ClinicalTrials.gov, NCT00600860, as is ongoing. FINDINGS: 2448 patients (the ESA-unexposed group [n=1265] and ESA-exposed group [n=1183]) were diagnosed before July 1, 2019; 1520 (62·1%) were male and 928 (37·9%) were female. Median follow-up time was 3·9 years (IQR 1·6-6·5). After applying eligibility criteria and propensity matching, there were 426 patients in the ESA-unexposed group and 744 patients in the ESA-exposed group. Median overall survival in the ESA exposed group was 44·9 months (95% CI 40·2-50·5) compared with 34·8 months (28·6-39·2) in the ESA unexposed group; the absolute difference was 10·1 months (95% CI 2·2-18·0; hazard ratio [HR] 0·70 [95% CI 0·59-0·83]; p<0·0001). Patients without RBCT in the presence or absence of ESA exposure maintained significantly better HRQoL than those with RBCT, irrespective of ESA exposure (linear mixed effect model of EQ-5d-3L index score, RBCT coefficient -0·04 [95% CI -0·06 to 0·03], p<0·0001; linear mixed effect model of VAS, -4·57 [-6·02 to -3·13], p<0·0001). INTERPRETATION: ESA treatment in patients with lower risk myelodysplastic syndromes significantly improves overall survival when started before or early after the onset of regular transfusion therapy. Avoiding RBCT is associated with significantly better HRQoL. FUNDING: H2020 European Research Council, Novartis Pharmacy B V Oncology Europe, Amgen, BMS/Celgene International, Janssen Pharmaceutica, Takeda Pharmaceuticals International, and Gilead Sciences.

Aberdeen Royal Infirmary Aberdeen UK

Centre Hospitalier de Perpignan Perpignan France

Centre Hospitalier Régional Universitaire de Nancy Hôpitaux de Brabois Vandèuvre lès Nancy France

Consorcio Hospital General Universitario de Valencia Valencia Spain

Epidemiology and Cancer Statistics Group Department of Health Sciences University of York York UK

General University Hospital of Alexandroupolis Alexandroupoli Greece

Hôpital Saint Louis Paris France

Institute of Hematology and Blood Transfusion Prague Czech Republic

Karolinska Institute Solna Sweden

Leeds Teaching Hospitals NHS Trust Leeds UK

Medizinische Universität Innsbruck Innsbruck Austria

Medizinische Universität Innsbruck Innsbruck Austria; Department of Public Health Health Services Research and Health Technology Assessment UMIT Tirol The Tyrolean Private University Hall in Tirol Austria

Radboud University Medical Center Nijmegen Netherlands

Sahlgrenska University Hospital Gothenburg Sweden

Tel Aviv Sourasky Medical Center Tel Aviv Yafo Israel

Universitätsklinikum Düsseldorf Düsseldorf Germany

University of Patras School of Medicine Patras Greece

University of Pavia and IRCCS Policlinico San Matteo Pavia Italy

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Blum S, Malcovati L. EHA Endorsement of the European Guidelines for Myelodysplastic Syndromes, MDS-RIGHT. Hemasphere. 2021;5:e631. PubMed PMC

Greenberg PL, Stone RM, Al-Kali A, et al. NCCN Guidelines® Insights: Myelodysplastic Syndromes, Version 3.2022. J Natl Compr Canc Netw. 2022;20:106–117. PubMed

Olsnes Kittang A. Guidelines for the diagnosis and treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. 2021. https://www.nmds.org/media/4/download

Gascón P, Krendyukov A, Mathieson N, Aapro M. Epoetin alfa for the treatment of myelodysplastic syndrome-related anemia: a review of clinical data, clinical guidelines, and treatment protocols. Leuk Res. 2019;81:35–42. PubMed

Platzbecker U, Symeonidis A, Oliva EN, et al. A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes. Leukemia. 2017;31:1944–1950. PubMed PMC

Fenaux P, Santini V, Spiriti MAA, et al. A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS. Leukemia. 2018;32:2648–2658. PubMed PMC

Jädersten M, Malcovati L, Dybedal I, et al. Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol. 2008;26:3607–3613. PubMed

Park S, Grabar S, Kelaidi C, et al. Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience. Blood. 2008;111:574–582. PubMed

Garelius HK, Johnston WT, Smith AG, et al. Erythropoiesis-stimulating agents significantly delay the onset of a regular transfusion need in nontransfused patients with lower-risk myelodysplastic syndrome. J Intern Med. 2017;281:284–299. PubMed PMC

Greenberg PL, Sun Z, Miller KB, et al. Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996) Blood. 2009;114:2393–2400. PubMed PMC

Haring Y, Goldschmidt N, Taha S, et al. MDS-related anemia is associated with impaired quality of life but improvement is not always achieved by increased hemoglobin level. J Clin Med. 2023;12 PubMed PMC

Park S, Greenberg P, Yucel A, et al. Clinical effectiveness and safety of erythropoietin-stimulating agents for the treatment of low- and intermediate-1-risk myelodysplastic syndrome: a systematic literature review. Br J Haematol. 2019;184:134–160. PubMed

Hoeks M, Yu G, Langemeijer S, et al. Impact of treatment with iron chelation therapy in patients with lower-risk myelodysplastic syndromes participating in the European MDS registry. Haematologica. 2020;105:640–651. PubMed PMC

Stauder R, Yu G, Koinig KA, et al. Health-related quality of life in lower-risk MDS patients compared with age- and sex-matched reference populations: a European LeukemiaNet study. Leukemia. 2018;32:1380–1392. PubMed PMC

Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–2405. PubMed

Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120:2454–2465. PubMed PMC

Greiner W, Weijnen T, Nieuwenhuizen M, et al. A single european currency for EQ-5D health states. Results from a six-country study. Eur J Health Econ. 2003;4:222–231. PubMed

Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 2014;33:1242–1258. PubMed PMC

Cole SR, Hernán MA. Adjusted survival curves with inverse probability weights. Comput Methods Programs Biomed. 2004;75:45–49. PubMed

Detry MA, Ma Y. Analyzing repeated measurements using mixed models. JAMA. 2016;315:407–408. PubMed

Snapinn SM, Jiang Q, Iglewicz B. Illustrating the impact of a time-varying covariate with an extended Kaplan-Meier estimator. Am Stat. 2005;59:301–307.

Bernard E, Tuechler H, Greenberg PL, et al. Molecular International Prognostic Scoring System for myelodysplastic syndromes. NEJM Evid. 2022;1 PubMed

Creignou M, Bernard E, Gasparini A, et al. Early transfusion patterns improve the Molecular International Prognostic Scoring System (IPSS-M) prediction in myelodysplastic syndromes. J Intern Med. 2024;296:53–67. PubMed

Park S, Kelaidi C, Sapena R, et al. Early introduction of ESA in low risk MDS patients may delay the need for RBC transfusion: a retrospective analysis on 112 patients. Leuk Res. 2010;34:1430–1436. PubMed

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