Reblozyl Approved as First-Line Treatment for Anemia in Lower-Risk Myelodysplastic Syndromes

The Food and Drug Administration (FDA) has approved Reblozyl^® (luspatercept-aamt) as first-line treatment of anemia in adults with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions and are erythropoiesis stimulating agent (ESA)-naïve.

The approval was based on interim results from the pivotal phase 3 COMMANDS trial (ClinicalTrials.gov Identifier: NCT03682536) that evaluated the efficacy and safety of luspatercept in 356 patients with anemia due to international prognostic scoring system (IPSS-R) very low-, low-, or intermediate-risk MDS or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN RS-T) in ESA-naïve patients who require regular RBC transfusions. 

Study participants were randomly assigned 1:1 to receive luspatercept or epoetin alfa for 24 weeks. All participants received best supportive care including RBC transfusions as needed. The primary endpoint was RBC transfusion independence (RBC-TI) for 12 weeks with a mean hemoglobin (Hgb) increase of at least 1.5g/dL.

Findings showed that 58.5% of patients treated with luspatercept achieved RBC-TI for at least 12 weeks with a mean Hgb increase of at least 1.5g/dL within the first 24 weeks vs 31.2% of patients treated with epoetin alfa (common rate difference, 26.6 [95% CI, 15.8-37.4]; P <.0001).

Additionally, a significantly greater proportion of patients in the luspatercept treatment arm met key secondary endpoints within the first 24 weeks of treatment vs the epoetin-alfa arm, including hematologic improvement-erythroid increase of at least 8 weeks (74.1% vs 51.3%, respectively; P <.0001); RBC-TI of at least 24 weeks (47.6% vs 29.2%, respectively; P =.0012); and RBC-TI of at least 12 weeks (66.7% vs 46.1%, respectively; P =.0003). 

As for safety, the most common adverse reactions for luspatercept were diarrhea, fatigue, hypertension, peripheral edema, nausea, and dyspnea.

Reblozyl is also approved for the treatment of anemia in adults with beta thalassemia who require RBC transfusions; and for the treatment of anemia failing an ESA and requiring 2 or more RBC units over 8 weeks in adults with very low- to intermediate-risk MDS-RS or with MDS/MPN-RS-T.