The Tapering Dose of Luspatercept in Patients With Lower-risk Myelodysplastic Syndromes

Inclusion Criteria:

• Male or female age ≥ 18 years
• Subject has diagnosis of MDS according to WHO classification that meets IPSS-R score ≤3.5
• Hemoglobin < 100g/L at baseline
• Refractory or intolerant to prior ESA treatment or EPO≥500U/L
• ECOG performance status ≤2
• Willing and able to comply with the requirements for this study and written informedconsent.

Exclusion Criteria:

• Platelet counts < 50 x 10^9/L
• Previously treated with either luspatercept or sotatercept
• Use any of the following prior to this study
• Immunomodulatory drugs such as lenalidomide [IMiD] for ≥4 weeks
• Immunosuppressive therapy [IST] for ≥4 weeks
• Demethylating agents [HMA] ≥ 1 cycle of treatment
• MDS associated with del 5q cytogenetic abnormality
• Secondary MDS, i.e. MDS that is known to have arisen as the result of chemical injuryor treatment with chemotherapy and/or radiation for other diseases.
• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies,or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding.
• Prior allogeneic or autologous stem cell transplant.
• Prior history of malignancies, other than MDS, unless the subject is free of thedisease (including completion of any active or adjuvant treatment for priormalignancy) for ≥ 5 years. However, subjects with the following history/concurrentconditions are allowed: basal or squamous cell carcinoma of the skin, superficialbladder cancer, prostate intraepithelial neoplasia, carcinoma in situ of the cervix orother indolent tumors.
• Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoingsigns/symptoms related to the infection without improvement despite appropriateantibiotics, antiviral therapy, and/or other treatment), known human immunodeficiencyvirus (HIV), known evidence of active infectious hepatitis B, and/or known evidence ofactive hepatitis C.
• Clinically significant cardiac disease, including any of the follow: uncontrolledangina pectoris, myocardial infarction, unstable cardiac arrhythmias, congestive heartfailure and New York Heart Association (NYHA) grade 2-4 cardiac failure.
• Abnormal liver function: two consecutive examinations with an interval of ≥1 weeksuggest that ALT and AST are 2.5 times higher than the upper limit of normal values
• Renal impairment: creatinine clearance <60ml/min
• Any severe and/or uncontrolled medical conditions or other conditions that couldaffect their participation in the study, including clinically significant cardiacdiseases, refractory hypertension, metabolic disorders and other diseases thatseriously affect the function of the gastrointestinal tract.
• Had a history of any psychiatric diseases, cerebrovascular disease or cognitivesequelae of head injury.
• Major surgery within 8 weeks prior to this study. Subjects must be completelyrecovered from any previous surgery prior to this study.
• Received attenuated vaccine in 4 weeks before enrollment.
• Participation in another clinical trial within 4 weeks before the start of this trial.
• History of severe allergic or anaphylactic reactions or hypersensitivity torecombinant proteins or excipients in the luspatercept.
• Pregnant or breast-feeding patients
• Patients considered to be ineligible for the study by the investigator for reasonsother than the above.