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Mechanism of disease

Impaired erythroid maturation contributes to ineffective erythropoiesis, resulting in low production of RBCs and anemia1,2

Impaired erythroid maturation contributes to ineffective erythropoiesis, resulting in low production of RBCs and anemia.

BFU-E, burst-forming unit erythroid; CFU-E, colony-forming unit erythroid; HSC, hematopoietic stem cell; TGF-β, transforming growth factor beta.

Mechanism of action

REBLOZYL restores erythropoiesis by increasing the number and improving the quality of mature RBCs2,6

REBLOZYL erythroid maturation

In preclinical models, REBLOZYL improved hemoglobin levels, RBC morphology, and other hematology parameters* associated with ineffective erythropoiesis5-7

*Other hematology parameters include reducing oxidative stress in erythrocytes, reducing accumulation of α-globin aggregates in erythrocyte membranes, and improving RBC life span.7

How REBLOZYL works is based on preclinical studies6

REBLOZYL - Mechanism of Action
REBLOZYL - Mechanism of Action

Watch the mechanism of action of REBLOZYL

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Erythropoiesis and ineffective erythropoiesisLuspatercept MOA



REBLOZYL is indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.

REBLOZYL is indicated for the treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).

REBLOZYL is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.




In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) REBLOZYL-treated patients. TEEs included deep vein thrombosis, pulmonary embolus, portal vein thrombosis, and ischemic stroke. Patients with known risk factors for thromboembolism (splenectomy or concomitant use of hormone replacement therapy) may be at further increased risk of thromboembolic conditions. Consider thromboprophylaxis in patients at increased risk of TEE. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly.


Hypertension was reported in 10.7% (61/571) of REBLOZYL-treated patients. Across clinical studies, the incidence of Grade 3 to 4 hypertension ranged from 1.8% to 8.6%. In patients with beta thalassemia with normal baseline blood pressure, 13 (6.2%) patients developed systolic blood pressure (SBP) ≥130 mm Hg and 33 (16.6%) patients developed diastolic blood pressure (DBP) ≥80 mm Hg. In adult patients with MDS with normal baseline blood pressure, 26 (29.9%) patients developed SBP ≥130 mm Hg and 23 (16.4%) patients developed DBP ≥80 mm Hg. Monitor blood pressure prior to each administration. Manage new or exacerbations of preexisting hypertension using anti-hypertensive agents.

Embryo-Fetal Toxicity

REBLOZYL may cause fetal harm when administered to a pregnant woman. REBLOZYL caused increased post-implantation loss, decreased litter size, and an increased incidence of skeletal variations in pregnant rat and rabbit studies. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the final dose.



  • Serious adverse reactions occurred in 3.6% of patients on REBLOZYL. Serious adverse reactions occurring in 1% of patients included cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in 1 patient treated with REBLOZYL who died due to an unconfirmed case of acute myeloid leukemia (AML)
  • Most common adverse reactions (at least 10% for REBLOZYL and 1% more than placebo) were headache (26% vs 24%), bone pain (20% vs 8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%)

Myelodysplastic Syndromes

  • Grade ≥3 (≥2%) adverse reactions included fatigue, hypertension, syncope and musculoskeletal pain. A fatal adverse reaction occurred in 5 (2.1%) patients
  • The most common (≥10%) adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis, and urinary tract infection


It is not known whether REBLOZYL is excreted into human milk or absorbed systemically after ingestion by a nursing infant. REBLOZYL was detected in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because many drugs are excreted in human milk, and because of the unknown effects of REBLOZYL in infants, a decision should be made whether to discontinue nursing or to discontinue treatment. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for 3 months after the last dose.

Please click here for full Prescribing Information for REBLOZYL.

References: 1. Liang R, Ghaffari S. Advances in understanding the mechanisms of erythropoiesis in homeostasis and disease. Br J Haematol. 2016;174(5):661-673. 2. Ponka P, Koury MJ, Sheftel AD. Erythropoiesis, hemoglobin synthesis, and erythroid mitochondrial iron homeostasis. In: Ferreira GC, ed. Handbook of Porphyrin Science: with Applications to Chemistry, Physics, Materials Science, Engineering, Biology and Medicine. Vol 27. Singapore: World Scientific Publishing Co.; 2014. 3. Lodish H, Flygare J, Chou S. From stem cell to erythroblast: regulation of red cell production at multiple levels by multiple hormones. IUBMB Life. 2010;62(7):492-496. 4. Fortunel NO, Hatzfeld A, Hatzfeld JA. Transforming growth factor-β: pleiotropic role in the regulation of hematopoiesis. Blood. 2000;96(6):2022-2036. 5. Suragani RN, Cadena SM, Cawley SM, et al. Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med. 2014;20(4):408-414. 6. REBLOZYL [Prescribing Information]. Summit, NJ: Celgene Corporation; 2020. 7. Suragani RNVS, Cawley SM, Li R. Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine β-thalassemia. Blood. 2014;123(25):3864-3872.