Study Evaluating Combination of Luspatercept in LR-MDS Without RS Having Failed or Being Ineligible to ESA

Inclusion Criteria: Patients must meet all of the following criteria to participate in the study: * Myelodysplastic syndrome according to current WHO classification * Age ≥ 18 years * Patients with lower risk MDS according to IPSS classification (LOW, INT-1) without RS who failed to achieved a response or who subsequently relapse after ESA (at least 60000 U EPO-a over at least 12weeks or equivalent), without disease progression (or ineligible to ESA defined by EPO \> 500 UI/l) * Hemoglobin \< 9 gr/dl or Transfusion dependant (at least 3 RBCs in 16 wk in at least 2 transfusion episodes) * Non del(5q) syndrome * Adequat renal function, defined by creatinine less than 1.5 times the upper limit of normal, creatinine clearance ≥ 40 mL/min (MDRD formula). * Adequat liver function, defined by total bilirubin and transaminases less than 1.5 times the upper limit of normal. * Patient is not known to be refractory to platelet transfusions. * Written informed consent. * Patient must understand and voluntarily sign consent form. * Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements. * ECOG performance status 0-2 at the time of screening. * A FCBP (female of childbearing potential) for this study was defined as a sexually mature woman who: (1) had not undergone a hysterectomy or bilateral oophorectomy; or (2) had not been naturally postmenopausal (amenorrhea following cancer therapy did not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). A FCBP participating in the study must: * Have had 2 negative pregnancy tests as verified by the investigator prior to starting IP (unless the screening pregnancy test was done within 72 hours of Cycle 1 Day 1). She must have had agreed to ongoing a monthly pregnancy testing during the course of the study and after EOT * If sexually active, agreed to have used, and been able to comply with, highly effective contraception\*\* without interruption, 5 weeks prior to starting IP, during treatment with IP (including dose interruptions), and for 12 weeks after discontinuation of IP. * \*\* Highly effective contraception was defined in this protocol as the following (information also appeared in the ICF): Hormonal contraception (eg, birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device, tubal ligation (tying your tubes), or a partner with a vasectomy * Male subjects must: Have agreed to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (eg, polyurethane), during sexual contact with a pregnant female or a FCBP while participating in the study, during dose interruptions, and for at least 12 weeks following IP discontinuation, even if he had undergone a successful vasectomy Exclusion Criteria: A patient meeting any of the following criteria is not eligible to participate in the study: * Severe infection or any other uncontrolled severe condition. * Uncontrolled hypertension * Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months. * del(5q) syndrome * Use of investigational agents within 30 days or any anticancer therapy (including IMiD) within 2 weeks before the study entry with the exception of hydroxyurea. The patient must have recovered at least a grade 1 from all acute toxicity from any previous therapy. * Use of EPO within 4 weeks before the study entry * Active cancer, or cancer during the year prior to trial entry other than basal cell carcinoma, or carcinoma in situ of the cervix or breast. * Patient already enrolled in another therapeutic trial of an investigational drug. * Known HIV infection or active hepatitis B or C. * Women who are or could become pregnant or who are currently breastfeeding. * Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form. * Patient eligible for allogeneic stem cell transplantation. * Known allergies to luspatercept or EPO or any of its excipients. * No affiliation to a health insurance system.