Luspatercept for Reducing the Number of Blood Transfusions in Patients with Lower Risk Myelodysplastic Syndromes

Inclusion Criteria

• Age >= 18 years; as MDS there is no significant experience with luspatercept in pediatric patients.
• Cohorts #1 and #2: Diagnosis of MDS according to World Health Organization (WHO) 2023 criteria and with low or intermediate (int)-1 risk by International Prognostic Scoring System (IPSS) or a score of =< 3.5 by IPSS-Revised (IPSS-R).
• 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.
• 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.
• MDS patients with either a platelet count of =< 100 K/uL and/or absolute neutrophil count (ANC) of =< 1.8 K/uL.
• Patient must have signed an informed consent and is willing to participate in the study.
• Total bilirubin =< 3 x upper limit normal (ULN).
• Aspartate aminotransferase (AST) or alanine transaminase (ALT) =< 3 x ULN.
• Serum creatinine clearance >= 40mL/min and no end/stage renal disease (using Cockcroft-Gault).
• Eastern Cooperative Oncology Group (ECOG) performance status </= 2.
• Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy (within 14 days of initiating study treatment).

Exclusion Criteria

• Active infection not adequately responding to appropriate antibiotics.
• Prior treatment with luspatercept or sotatercept.
• Female patients who are pregnant or lactating.
• Patients with reproductive potential who are unwilling to following contraception requirements (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 with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study. Reproductive potential is defined as no previous surgical sterilization or females that are not post-menopausal for 12 months.
• Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
• History of an active malignancy within the past 2 years prior to study entry, with the exception of: a. Adequately treated in situ carcinoma of the cervix uteri b. Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin or any other malignancy with a life expectancy of more than 2 years.