Luspatercept With or Without Hydroxyurea for the Treatment of Myelodysplastic/Myeloproliferative Neoplasms With Ring Sideroblasts and Thrombocytosis or Unclassifiable With Ring Sideroblasts

PRIMARY OBJECTIVE: I. To document the erythroid response rate assessed as per the 2015 International Working Group (IWG) myelodysplastic (MDS)/myeloproliferative neoplasms (MPN) response criteria. SECONDARY OBJECTIVES: I. To document response duration, time to acute myeloid leukemia (AML) transformation, AML-free survival (LFS) and overall survival (OS) in patients with MDS/MPN-with ring sideroblasts (RS) and thrombocytosis (T) and MDS/MPN-unclassifiable (U)U with RS. II. To document safety of luspatercept (luspatercept-aamt) in patients with MDS/MPN-RS-T and MDS/MPN-U with RS. EXPLORATORY OBJECTIVE: I. To assess overall health-related quality of life as measured by Hematological Malignancy Specific Patient-Reported Outcome Measure (HM-PRO). CORRELATIVE RESEARCH OBJECTIVE: I: To find an effective biomarker of response to luspatercept-aamt. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT A: Patients receive luspatercept subcutaneously (SC) on day 1. Cycles repeat every 21 days for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone marrow biopsy and aspirate at baseline and on study. COHORT B: Patients receive luspatercept SC on day 1 and hydroxyurea orally (PO) on days 1-21. Cycles repeat every 21 days for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone marrow biopsy and aspirate at baseline and on study. After completion of study treatment, patients are followed up every 3 months.