EFFICACY and safety: primary endpoint

Superior rates of response: Hgb increase and transfusion independence2

Primary composite endpoint: Hgb increase ≥1.5 g/dL and RBC-TI for at least 12 weeks2

During Weeks 1-24, patients receiving REBLOZYL had a 58.5% response rate (n=86/147; 95% Cl: 50.1, 66.6) vs 31.2% in patients receiving epoetin alfa (n=48/154; 95% Cl: 24.0, 39.1). Common rate difference (95% CI) was 26.6 (15.8, 37.4), P<0.0001. Nearly 2X the response rate vs epoetin alfa.

Key secondary endpoints included HI-E per IWG ≥8 weeks (Weeks 1-24): REBLOZYL 74.1% (109/147), epoetin alfa 51.3% (n=79/154); RBC-TI for 24 weeks (Weeks 1-24): REBLOZYL 47.6% (n=70/147), epoetin alfa 29.2% (n=45/154); and RBC-TI for ≥12 weeks (Weeks 1-24): REBLOZYL 66.7% (n=98/147), epoetin alfa 46.1% (n=71/154).2

Callout Dots

It's not if, but when—
80% of all patients receiving REBLOZYL had their dose increased at least once.3

Callout Dots

Patient population and study design

REBLOZYL was studied head-to-head vs an ESA2

COMMANDS: A Phase 3, open-label, randomized, active-controlled, head-to-head trial of REBLOZYL vs epoetin alfa in anemia due to LR-MDS in ESA-naive patients2,4

Select graphic view or text view to explore data

Patient population (N=365): Adults greater than or equal to 18 years of age; IPSS-R very low-, low-, or intermediate-risk MDS; RS-positive and RS-negative; ESA-naive; endogenous sEPO less than 500 U/L; requiring RBC transfusions for Hgb less than or equal to 9 g/dL with symptoms or Hgb less than or equal to 7 g/dL without symptoms and 2 to 6 units of RBCs within 8 weeks prior to randomization. Patients with del(5q) and those previously treated with disease-modifying agents or HMAs were excluded. Patients were randomized 1:1 to either REBLOZYL or epoetin alfa. Patients in the REBLOZYL arm received 1 mg/kg SC Q3W, with titration up to max 1.75 mg/kg if needed to achieve response (n=178). Patients in the epoetin alfa arm received 450 IU/kg SC QW with titration up to 1,050 IU/kg if needed (maximum total dose of 80,000 IU) (n=178). Both treatments were dose modified, targeting Hgb between 10-12 g/dL and TI. The composite primary endpoint for any consecutive 12-week period during Weeks 1-24 were RBC-TI and mean improvement in Hgb by at least 1.5 g/dL. The key secondary endpoints were HI-E response per IWG greater than or equal to 8 weeks (Weeks 1-24); RBC-TI for 24 weeks (Weeks 1-24); and RBC-TI for greater than or equal to 12 weeks (Weeks 1-24). Other secondary endpoints were mean Hgb increase greater than or equal to 1.5 g/dL (Weeks 1-24); duration of RBC-TI greater than or equal to 12 weeks (Weeks 1-EOT); time to first RBC transfusion (Week 1-EOT); and Hgb change from baseline over 24 weeks (Weeks 1-24). Refer to references 2,4,5 and 6 and the dagger and double dagger footnotes for details.

Patient Population (N=356)2,4,5

  • Adults ≥18 years of age
  • IPSS-R very low-, low-, or intermediate-risk MDS
  • RS-positive and RS-negative
  • ESA-naive
  • Endogenous sEPO <500 U/L
  • Requiring RBC transfusion for Hgb ≤9 g/dL with symptoms or Hgb ≤7 g/dL without symptoms and 2 to 6 units of RBCs within 8 weeks prior to randomization
  • Excluded: patients with del(5q) and those previously treated with disease-modifying agents or HMAs

Randomized 1:1

REBLOZYL2

1 mg/kg SC Q3W, with titration up to max 1.75 mg/kg if needed to achieve a response (n=178)

EPOETIN ALFA2,4†

450 IU/kg SC QW with titration up to 1,050 IU/kg if needed (maximum total dose of 80,000 IU) (n=178)

Both treatments were dose modified targeting Hgb between 10-12 g/dL and TI6

All patients received BSC, which included RBC transfusions as needed2

Composite primary endpoint2

For any consecutive 12 week period during Weeks 1 to 24:

  • RBC-TI
    and
  • Mean improvement in Hgb by at least 1.5 g/dL

Key secondary endpoints2

  • HI-E response per IWG ≥8 weeks
    (Weeks 1-24)
  • RBC-TI for 24 weeks (Weeks 1-24)
  • RBC-TI for ≥12 weeks (Weeks 1-24)

Other secondary endpoints2,4

  • Mean Hgb increase ≥1.5 g/dL (Weeks 1-24)
  • Duration of RBC-TI ≥12 weeks (Weeks 1-EOT)
  • Time to first RBC transfusion (Week 1-EOT)
  • Hgb change from baseline over 24 weeks (Weeks 1-24)

*>90% of study participants were outside of the United States and used a non-US-licensed epoetin alfa product. Direct comparisons between REBLOZYL and US-licensed epoetin alfa product have not been established.2

Interim analysis of COMMANDS reported.2

Baseline disease characteristics

Balanced across study arms events in pivotal Phase 3 COMMANDS trial2

COMMANDS Trial baseline disease characteristics. Tap over to text view tab for details.

Baseline Disease Characteristics for REBLOZYL (n=178) and Epoetin Alfa (n=178)

Hemoglobin (g/dL)

  • Median (min, max): REBLOZYL 7.80 (4.7, 9.2) and Epoetin Alfa 7.80 (4.5, 10.2)

Serum EPO (U/L)

  • Median (min, max): REBLOZYL 78.7 (7.8, 495.8) and Epoetin Alfa 85.9 (4.6, 462.5)

A majority of patients had sEPO levels ≤200 U/L4

IPSS-R risk classification at baseline – n(%)

  • Very low: REBLOZYL 16 (9.0) and Epoetin Alfa 17 (9.6)
  • Low: REBLOZYL 126 (70.8) and Epoetin Alfa 131 (73.6)
  • Intermediate: REBLOZYL 34 (19.1) and Epoetin Alfa 28 (15.7)
  • High: REBLOZYL 1 (0.6) and Epoetin Alfa 0 (0)
  • Missing: REBLOZYL 1 (0.6) and Epoetin Alfa 2 (1.1)

RS status (per WHO criteria) – n (%)

  • RS-positive REBLOZYL 130 (73.0) and Epoetin Alfa 128 (71.9)
  • RS-negative REBLOZYL 48 (27.0) and Epoetin Alfa 49 (27.5)

COMMANDS had the largest number of RS- patients of any Phase 3 LR-MDS study7-9

  • Missing: REBLOZYL 0 (0) and Epoetin Alfa 1 (0.6)

SF3B1 mutation status – n (%)

  • Mutated: REBLOZYL 111 (62.4) and Epoetin Alfa 99 (55.6)
  • Non-mutated: REBLOZYL 65 (36.5) and Epoetin Alfa 72 (40.4)
  • Missing: REBLOZYL 2(1.1) and Epoetin Alfa 7 (3.9)

BSC=best supportive care; CI=confidence interval; EOT=end of treatment; EPO=erythropoietin; ESA=erythropoiesis-stimulating agent; Hgb=hemoglobin; HI-E=hematologic improvement-erythroid; HMA=hypomethylating agent; IPSS-R=Revised International Prognostic Scoring System; IWG=International Working Group; LR-MDS=lower-risk myelodysplastic syndromes; MDS=myelodysplastic syndromes; QW=once a week; Q3W=once every 3 weeks; RBC=red blood cell; RBC-TI=red blood cell transfusion independence; RS=ring sideroblast; SC=subcutaneous; sEPO=serum erythropoietin; TI=transfusion independence; WHO=World Health Organization.

Explore safety data

References: 1. REBLOZYL [US Prescribing Information]. Summit, NJ: Celgene Corporation; 2026. 2. Santini V, Zeidan AM, Platzbecker U, et al. Clinical benefit of luspatercept treatment in transfusion-dependent, erythropoiesis-stimulating agent-naive patients with very low-, low- or intermediate-risk myelodysplastic syndromes in the COMMANDS trial. Poster presented at: European Hematology Association (EHA) Hybrid Congress. June 13-16, 2024. Madrid, Spain. 3. Platzbecker U, Della Porta MG, Santini V, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. Lancet. 2023;402(10399):373-385. 4. Platzbecker U, Della Porta MG, Santini V, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial (supplementary appendix). Lancet. 2023; published online June 10, 2023. https://doi.org/10.1016/S0140-6736(23)00874-7 5. Data on file. BMS-REF-00730-2007. Princeton, NJ: Bristol-Myers Squibb Company; 2024. 6. Fenaux P, Santini V, Spiriti MAA, et al. A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-a in anemic patients with low-risk MDS. Leukemia. 2018;32(12):2648-2658. 7. Greenberg PL, Tuechler H, Schanz J, et al. Revised International Prognostic Scoring System for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465. 8. Garcia-Manero G, Platzbecker U, Santini V, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive patients with transfusion-dependent lower-risk myelodysplastic syndromes: full analysis of the COMMANDS trial. Presented at: American Society of Hematology (ASH) Annual Meeting and Exposition. December 9-12, 2023. San Diego, CA. Abstract 193.

References

INDICATIONS

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

REBLOZYL® (luspatercept-aamt) is indicated for the treatment of anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions.

REBLOZYL® (luspatercept-aamt) is indicated for the treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell (RBC) 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.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Thrombosis/Thromboembolism

In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) of 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

Hypertension was reported in 11.4% (63/554) of REBLOZYL-treated patients. Across clinical studies, the incidence of Grade 3 to 4 hypertension ranged from 2% to 9.6%. 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 ESA-refractory or -intolerant adult patients with MDS with normal baseline blood pressure, 26 (30%) patients developed SBP ≥130 mm Hg and 23 (16%) patients developed DBP ≥80 mm Hg. In ESA-naïve adult patients with MDS with normal baseline blood pressure, 23 (36%) patients developed SBP ≥140 mm Hg and 11 (6%) patients developed DBP ≥80 mm Hg. Monitor blood pressure prior to each administration. Manage new or exacerbations of preexisting hypertension using anti-hypertensive agents.

Extramedullary Hematopoietic (EMH) Masses

In adult patients with transfusion-dependent beta thalassemia, EMH masses were observed in 3.2% of REBLOZYL-treated patients, with spinal cord compression symptoms due to EMH masses occurring in 1.9% of patients (BELIEVE and REBLOZYL long-term follow-up study).

In a study of adult patients with non-transfusion-dependent beta thalassemia, a higher incidence of EMH masses was observed in 6.3% of REBLOZYL-treated patients vs. 2% of placebo-treated patients in the double-blind phase of the study, with spinal cord compression due to EMH masses occurring in 1 patient with a prior history of EMH. REBLOZYL is not indicated for use in patients with non-transfusion-dependent beta thalassemia.

Possible risk factors for the development of EMH masses in patients with beta thalassemia include history of EMH masses, splenectomy, splenomegaly, hepatomegaly, or low baseline hemoglobin (<8.5 g/dL). Signs and symptoms may vary depending on the anatomical location. Monitor patients with beta thalassemia at initiation and during treatment for symptoms and signs or complications resulting from the EMH masses and treat according to clinical guidelines. Discontinue treatment with REBLOZYL in case of serious complications due to EMH masses. Avoid use of REBLOZYL in patients requiring treatment to control the growth of EMH masses.

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.

ADVERSE REACTIONS

Beta-Thalassemia

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%).

ESA-naïve adult patients with Myelodysplastic Syndromes

Grade >3 (>2%) adverse reactions included hypertension and dyspnea.

The most common (>10%) all-grade adverse reactions included diarrhea, fatigue, hypertension, peripheral edema, nausea, and dyspnea.

ESA-refractory or -intolerant adult patients with 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.

LACTATION

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.

DRUG ABUSE POTENTIAL

Abuse: Abuse of REBLOZYL may be seen in athletes for the effects on erythropoiesis. Misuse of drugs that increase erythropoiesis, such as REBLOZYL, by healthy persons may lead to polycythemia, which may be associated with life-threatening cardiovascular complications.

For more information, please see US Full Prescribing Information for REBLOZYL.

2007-US-2500414     3/26

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2007-US-2400451   12/2024