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REBLOZYL® (luspatercept-aamt) logo
LR-MDS (FIRST-LINE) LR-MDS-RS (SECOND-LINE) BETA-THALASSEMIA

This website is intended for US Healthcare Professionals.

REBLOZYL® (luspatercept-aamt) logo
INDICATIONS

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.

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Luspatercept-aamt (REBLOZYL®) is recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a first-line treatment option for symptomatic anemia in lower-risk MDS1*

EFFICACY AND SAFETY: SUBGROUPS

REBLOZYL delivered durable RBC-TI1

Durable transfusion-free time exhibited across all patients1

EFFICACY AND SAFETY: SUBGROUPS

REBLOZYL delivered durable RBC-TI1

Durable transfusion-free time exhibited across all patients1

Secondary endpoint: Median duration of RBC-TI ≥12 weeks (Week 1-EOT)

Duration of RBC-TI for ≥12 weeks2

Primary composite endpoints in 1-24 weeks for Reblozyl vs Epoetin Alfa in Phase 3 COMMANDS trial
View data graph icon View KM Curve

Analysis limitations: Duration of RBC-TI ≥12 weeks was not powered to detect statistical significance.1

Data cutoff date: August 2022.

From the full analysis 48-week follow-up

REBLOZYL results across key subgroups2

Response rates of the preplanned subgroup analysis of RBC-TI for ≥24 weeks (Weeks 1-48)2

Preplanned subgroup analysis Preplanned subgroup analysis

Analysis limitations:

  • Subgroup analyses were performed for the primary and key secondary efficacy endpoints. Formal hypothesis testing was not performed
  • These analyses should not be interpreted to determine treatment differences between arms in these subgroups because of limited sample size, lack of statistical hypothesis testing, and the increased probability of a false-positive finding

P<0.0001.

Data cutoff date: September 2023.

From the full analysis

Nearly 80% of patients in COMMANDS had baseline sEPO ≤200 U/L2†

Among patients with baseline sEPO ≤200 U/L

RBC-TI for ≥12 weeks and mean Hgb increase ≥1.5 g/dL3

RBC-TI for ≥12 weeks and mean Hgb increase ≥1.5 g/dL Among patients with baseline sEPO ≤200 U/L

Duration of RBC-TI for ≥12 weeks2

Duration of RBC-TI for ≥12 weeks Among patients with baseline sEPO ≤200 U/L
View data graph icon View KM Curve

On REBLOZYL, ~38% of EPO >200 patients achieved a mean Hgb increase of ≥1.5 g/dL and TI for ≥12 weeks vs ~11% of patients on epoetin alfa. REBLOZYL patients also achieved a mean of 1 year of TI compared to patients on epoetin alfa who only experienced a mean of 0.5 years of TI.2,3

The primary endpoint for Weeks 1-24, RBC-TI ≥12 weeks with concurrent mean Hgb increase ≥1.5 g/dL, was achieved by 86 (58.5%) patients in the REBLOZYL arm versus 48 (31.2%) patients in the epoetin alfa arm (P<0.0001).4

Analysis limitations:

  • Subgroup analyses were performed for the primary and key secondary efficacy endpoints. Formal hypothesis testing was not performed
  • These analyses should not be interpreted to determine treatment differences due to limited sample size, lack of statistical hypothesis testing, and increased probability of a false-positive finding

145 patients in the REBLOZYL arm and 144 patients in the epoetin alfa arm had sEPO ≤200 U/L.2


Data cutoff date: March 2023.

From the full analysis 48-week follow-up‡

COMMANDS had 99 RS- patients, the most of any Phase 3, LR-MDS study3,5,6

Among RS- patients

RBC-TI for ≥12 weeks and mean Hgb increase ≥1.5 g/dL3

RBC-TI for ≥12 weeks and mean Hgb increase ≥1.5 g/dL among RS- patients

Duration of RBC-TI for ≥12 weeks2

Duration of RBC-TI for ≥12 weeks among RS- patients
View data graph icon View KM Curve
Callout DotsCallout Dots

Duration for REBLOZYL arm was not reached (NR) because >50% of patients were still transfusion independent at time of analysis2

Callout DotsCallout Dots

The primary endpoint for Weeks 1-24, RBC-TI ≥12 weeks with concurrent mean Hgb increase ≥1.5 g/dL, was achieved by 86 (58.5%) patients in the REBLOZYL arm versus 48 (31.2%) patients in the epoetin alfa arm (P<0.0001).4

Analysis limitations:

  • Subgroup analyses were performed for the primary and key secondary efficacy endpoints. Formal hypothesis testing was not performed
  • These analyses should not be interpreted to determine treatment differences due to limited sample size, lack of statistical hypothesis testing, and increased probability of a false-positive finding

Exploratory endpoint.


Data cutoff date: September 2023.

Watch clinical experts discuss treating key patient groups

Using sEPO ≤200 as a parameter in the LR-MDS treatment algorithm

George Yaghmour, MD

USC Norris Comprehensive Cancer Center & Hospital

Los Angeles, CA

Using sEPO ≤200 as a parameter video thumbnail

View video transcript

Clinical response and duration in the RS- subgroups

Jamie Koprivnikar, MD

John Theurer Cancer Center Hackensack University Medical Center

Hackensack, NJ

Clinical response and duration video thumbnail

View video transcript

CI=confidence interval; EOT=end of treatment; EPO=erythropoietin; Hgb=hemoglobin; ITT=intent to treat; KM=Kaplan-Meier; LR-MDS=lower-risk myelodysplastic syndromes; MDS=myelodysplastic syndromes; RBC=red blood cell; RBC-TI=red blood cell transfusion independent; RS=ring sideroblast; sEPO=serum erythropoietin; TB=transfusion burden; TI=transfusion independence.

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.

Please click here for US Full Prescribing Information for REBLOZYL.

References: 1. 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 2. 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. 3. Data on file. BMS-REF-ACE-536-00689. Princeton, NJ: Bristol-Myers Squibb Company; 2024. 4. REBLOZYL [US Prescribing Information]. Summit, NJ: Celgene Corporation; 2024. 5. 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. 6. Greenberg PL, Sun Z, Miller KB, et al. Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996). Blood. 2009;144(12):2393-2400.

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GLOBAL Bristol Myers SquibbTM logo

REBLOZYL® is a trademark of Celgene Corporation, a Bristol Myers Squibb company.
Access Support® is a trademark of Bristol-Myers Squibb Company.
REBLOZYL® is licensed from Merck & Co., Inc., Rahway, NJ, USA and its affiliates.

© 2024 Bristol-Myers Squibb Company.
2007-US-2400257 10/2024

References: 1. 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 2. 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. 3. Data on file. BMS-REF-ACE-536-00689. Princeton, NJ: Bristol-Myers Squibb Company; 2024. 4. REBLOZYL [US Prescribing Information]. Summit, NJ: Celgene Corporation; 2024. 5. 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. 6. Greenberg PL, Sun Z, Miller KB, et al. Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996). Blood. 2009;144(12):2393-2400.