Plasmatic Biomarkers Associated With Short-term Luspatercept Treatment of Lower Risk Myelodysplastic Syndromes (MDS) Patients

Summary

Our project aims to identify metabolites and biomarkers associated with luspatercept-related asthenia in a prospective French study of low-risk MDS patients treated per EMA guidelines. This is a prospective cohort of patients with MDS treated with luspatercept. The main comparisons will consist in exploring differences in biomarkers plasma levels between patients experiencing fatigue after luspatercept initiation, vs those who do not.

Timeline

Start

2026-11

Primary completion

2031-05

Completion

2031-11

Publications

• Background Mathieu M, Friedrich C, Ducrot N, Zannoni J, Sylvie T, Jerraya N, Rousseaux S, Chuffart F, Kosmider O, Karim Z, Park S. Luspatercept (RAP-536) modulates oxidative stress without affecting mutation burden in myelodysplastic syndromes. Ann Hematol. 2022 Dec;101(12):2633-2643. doi: 10.1007/s00277-022-04993-7. Epub 2022 Oct 5.
• Background Meunier M, Guttin A, Ancelet S, Laurin D, Zannoni J, Lefebvre C, Tondeur S, Persoons V, Pezet M, Pernet-Gallay K, Chuffart F, Rousseaux S, Testard Q, Thevenon J, Jouzier C, Deleuze JF, Laulagnier K, Sadoul R, Chatellard C, Hainaut P, Polack B, Cahn JY, Issartel JP, Park S. Extracellular vesicles from myelodysplastic mesenchymal stromal cells induce DNA damage and mutagenesis of hematopoietic stem cells through miRNA transfer. Leukemia. 2020 Aug;34(8):2249-2253. doi: 10.1038/s41375-020-0738-8. Epub 2020 Feb 12. No abstract available.
• Background Jouzier C, Cherait A, Cony-Makhoul P, Hamel JF, Veloso M, Thepot S, Cluzeau T, Stamatoullas A, Garnier A, Guerci-Bresler A, Dimicoli-Salazar S, Pica GM, Cheze S, Santana C, Chermat F, Fenaux P, Park S. Red blood cell transfusion burden in myelodysplastic syndromes (MDS) with ring Sideroblasts (RS): A retrospective multicenter study by the Groupe Francophone des Myelodysplasies (GFM). Transfusion. 2022 May;62(5):961-973. doi: 10.1111/trf.16884. Epub 2022 Apr 22.
• Background Raskovalova T, Jacob MC, Park S. Myelodysplastic Syndromes. N Engl J Med. 2020 Dec 24;383(26):2590. doi: 10.1056/NEJMc2032391. No abstract available.
• Background Kaphan E, Laurin D, Lafeuillade B, Drillat P, Park S. Impact of transfusion on survival in patients with myelodysplastic syndromes: Current knowledge, new insights and transfusion clinical practice. Blood Rev. 2020 May;41:100649. doi: 10.1016/j.blre.2019.100649. Epub 2019 Dec 18.
• Background Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Diez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Gotze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellstrom-Lindberg E, Zeidan AM, Ades L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. N Engl J Med. 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892.
• Background Park S, Kosmider O, Maloisel F, Drenou B, Chapuis N, Lefebvre T, Karim Z, Puy H, Alary AS, Ducamp S, Verdier F, Bouilloux C, Rousseau A, Jacob MC, Debliquis A, Charpentier A, Gyan E, Anglaret B, Leyronnas C, Corm S, Slama B, Cheze S, Laribi K, Ame S, Rose C, Lachenal F, Toma A, Pica GM, Carre M, Garban F, Mariette C, Cahn JY, Meunier M, Herault O, Fenaux P, Wagner-Ballon O, Bardet V, Dreyfus F, Fontenay M. Dyserythropoiesis evaluated by the RED score and hepcidin:ferritin ratio predicts response to erythropoietin in lower-risk myelodysplastic syndromes. Haematologica. 2019 Mar;104(3):497-504. doi: 10.3324/haematol.2018.203158. Epub 2018 Oct 4.
• Background Della Porta MG, Garcia-Manero G, Santini V, Zeidan AM, Komrokji RS, Shortt J, Valcarcel D, Jonasova A, Dimicoli-Salazar S, Tiong IS, Lin CC, Li J, Zhang J, Pilot R, Kreitz S, Pozharskaya V, Keeperman KL, Rose S, Prebet T, Lai Y, Degulys A, Paolini S, Cluzeau T, Fenaux P, Platzbecker U. Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial. Lancet Haematol. 2024 Sep;11(9):e646-e658. doi: 10.1016/S2352-3026(24)00203-5. Epub 2024 Jul 19.

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Indications