A Pilot, Open-Label Study of Luspatercept for Patients With Lower Risk Myelodysplastic Syndromes (MDS)

Inclusion Criteria:

1. Age ≥ 18 years; as MDS there is no significant experience with luspatercept inpediatric patients

2. Cohorts #1 and #2: Diagnosis of MDS according to WHO 2023 criteria (5) and with lowor 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 atleast 2 units of packed red blood cells (PRBCs) for a hemoglobin of less than 8.0g/dL during an 8-week period prior to study enrollment.

4. Cohort #1: Patients with symptomatic anemia that are transfusion independent definedas 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 thestudy.

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 (usingCockcroft-Gault).

9. ECOG performance status </=2.

Exclusion Criteria:

1. Active infection not adequately responding to appropriate antibiotics.

2. Prior treatment with luspatercept or sotarcetept

3. Female patients who are pregnant or lactating.

4. Patients with reproductive potential who are unwilling to following contraceptionrequirements (including condom use for males with sexual partners, and for females:prescription oral contraceptives [birth control pills], contraceptive injections,intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam withcondoms or diaphragm], contraceptive patch, or surgical sterilization) throughoutthe study. Reproductive potential is defined as no previous surgical sterilizationor females that are not post-menopausal for 12 months.

5. Female patients with reproductive potential who do not have a negative urine orblood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.

6. History of an active malignancy within the past 2 years prior to study entry, withthe exception of: a. Adequately treated in situ carcinoma of the cervix uteri b.Adequately treated basal cell carcinoma or localized squamous cell carcinoma of theskin or any other malignancy with a life expectancy of more than 2 years.

7. Patients receiving any other concurrent investigational agent or chemotherapy,radiotherapy, or immunotherapy (within 14 days of initiating study treatment).