To learn if luspatercept is more effective in helping to reduce the number of blood transfusions needed by patients with LR-MDS.

Objectives:

Primary Objectives:

• To assess the clinical activity and safety of luspatercept in patients with transfusion independent lower risk MDS
• To assess the clinical activity and safety of luspatercept in patients with transfusion dependent lower risk MDS
• To study the effects on hematopoeisis of luspatercept in patients treated on this study

Secondary Objectives:

• To assess the duration of response of patients with treated with luspatercept in this study
• To assess the overall survival and time to transformation of patients with treated with luspatercept in this study
• To assess transfusion free survival period in patients that were transfusion independent treated with luspatercept in this study
• To measure trends in neutrophil and platelet counts in patients treated in this study

Inclusion Criteria:

1. Age ≥ 18 years; as MDS there is no significant experience with luspatercept in pediatric patients
2. Cohorts #1 and #2: Diagnosis of MDS according to WHO 2023 criteria (5) and with low or int-1 risk by IPSS or a score of ≤ 3.5 by IPSS-R.(3, 22)
3. Cohort #2: Patient defined as transfusion dependent by documentation of receiving at least 2 units of packed red blood cells (PRBCs) for a hemoglobin of less than 8.0 g/dL during an 8-week period prior to study enrollment.
4. Cohort #1: Patients with symptomatic anemia that are transfusion independent defined as not requiring a transfusion for a hemoglobin of less than 8.0 g/dL during an 8-week period prior to study enrollment.
5. MDS patients with either a platelet count of ≤100 K/uL and/or ANC of ≤1.8 K/uL
6. Patient must have signed an informed consent and is willing to participate in the study.
7. Adequate hepatic function with total bilirubin ≤3 x ULN, AST or ALT ≤3xULN.
8. Serum creatinine clearance ≥40mL/min and no end/stage renal disease (using Cockcroft-Gault).
9. ECOG performance status \