This website is intended for US Healthcare Professionals.

Indications US Full Prescribing Information Patient Information Visit Patient Site BMS Connect
REBLOZYL® (luspatercept-aamt) logo

This website is intended for US Healthcare Professionals.

REBLOZYL® (luspatercept-aamt) logo
INDICATIONS

INDICATIONS

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.

Request a Rep

PATIENT IDENTIFICATION: IMPORTANCE OF TESTING

Ring sideroblasts can be evaluated using a bone marrow aspirate, a blood clot (from a bone aspirate), or a bone marrow trephine biopsy1,2

Ring sideroblast in bone marrow Ring sideroblast in bone marrow

For illustrative purposes only.

Methods to assess ring sideroblasts in cases with inadequate particles on aspirate for iron staining2:

  • In situations where a bone marrow aspirate is inadequate due to being aparticulate, it may not be possible to make an accurate assessment of ring sideroblasts
  • If the bone marrow aspirate is aparticulate, iron staining for ring sideroblasts can also be performed on a blood clot or a bone marrow trephine biopsy

Bone marrow smear demonstrating ring sideroblasts

Bone marrow smear showing ring sideroblasts

Bone marrow trephine biopsy demonstrating ring sideroblasts

Bone marrow trephine biopsy showing ring sideroblasts

Blood clot from a bone marrow aspirate demonstrating ring sideroblasts

Blood clot from a bone marrow aspirate showing ring sideroblasts

Inadequate/particulate bone marrow smear

Inadequate/particulate bone marrow smear

A pathologist’s quantitative assessment of ring sideroblasts and SF3B1 mutation status is critical to diagnosing patients with MDS-RS3,4

≥5% Ring sideroblasts

Assessment of ring sideroblasts for potential MDS-RS diagnosis

Presence of SF3B1

Assessment of ring sideroblasts for potential MDS-RS diagnosis

Assessment of ring sideroblasts for potential MDS-RS diagnosis Potential MDS-RS diagnosis

OR

≥15%Ring sideroblasts

Assessment of ring sideroblasts for potential MDS-RS diagnosis

Assessment of ring sideroblasts for potential MDS-RS diagnosisPotential MDS-RS diagnosis

cDNA=complementary DNA; ddPCR=droplet digital PCR; DNA=deoxyribonucleic acid; NGS=next-generation sequencing; PCR=polymerase chain reaction; TATs=turnaround times.

REBLOZYL is approved for patients with MDS-RS who are failing an ESA and require ≥2 RBC units/8 weeks5

There is currently a degree of variability in how pathologists describe the presence of ring sideroblasts in pathology reports6

  • Ring sideroblasts quantification should be included on the lab report in addition to the assessment of SF3B1 mutation status3,4
  • Quantitative reporting is critical to identifying patients with MDS-RS. REBLOZYL is approved specifically for patients with MDS-RS–associated anemia5
  • Variability in reporting of bone marrow specimens may result in incomplete or misleading information6

There is a strong link between MDS-RS, MDS/MPN-RS-T, and an SF3B1 mutation4

Proportion of patients with an SF3B1 mutation7

Proportion of patients with an SF3B1 mutation Proportion of patients with an SF3B1 mutation

79%

of patients with MDS-RS also have an SF3B1 mutation

The presence of an SF3B1 mutation and RS ≥5% could identify a diagnosis of MDS-RS and indicate the patient may be eligible for REBLOZYL therapy4,5

A range of different technologies can be used by pathologists to test for SF3B1 mutations8-13

ddPCR8,9

  • ddPCR works by partitioning a sample of DNA or cDNA into many individual, parallel PCR reactions
  • This is a relatively new technology that can provide short TATs or laboratories

Real-time PCR9,10

  • Real-time PCR can be used for both qualitative and quantitative assays
  • This method produces faster TATs than other methods of sequencing

Sanger sequencing9,11

  • Sanger sequencing is a well-established but comparably expensive method adopted by laboratories
  • TAT is 1-2 days

NGS9,12,13

  • NGS can analyze numerous genes simultaneously and is the most frequently used technology for SF3B1 testing
  • This is a relatively costly method and generally takes the laboratories ~2-21 days to report

cDNA=complementary DNA; ddPCR=droplet digital PCR; DNA=deoxyribonucleic acid; NGS=next-generation sequencing;
PCR=polymerase chain reaction; TATs=turnaround times.

PATIENT IDENTIFICATION: IMPORTANCE OF TESTING

Ring sideroblasts can be evaluated using a bone marrow aspirate, a blood clot (from a bone aspirate), or a bone marrow trephine biopsy1,2

Ring sideroblast in bone marrow Ring sideroblast in bone marrow

For illustrative purposes only.

Methods to assess ring sideroblasts in cases with inadequate particles on aspirate for iron staining2:

  • In situations where a bone marrow aspirate is inadequate due to being aparticulate, it may not be possible to make an accurate assessment of ring sideroblasts
  • If the bone marrow aspirate is aparticulate, iron staining for ring sideroblasts can also be performed on a blood clot or a bone marrow trephine biopsy

Bone marrow smear demonstrating ring sideroblasts

Bone marrow smear showing ring sideroblasts

Bone marrow trephine biopsy demonstrating ring sideroblasts

Bone marrow trephine biopsy showing ring sideroblasts

Blood clot from a bone marrow aspirate demonstrating ring sideroblasts

Blood clot from a bone marrow aspirate showing ring sideroblasts

Inadequate/particulate bone marrow smear

Inadequate/particulate bone marrow smear

A pathologist’s quantitative assessment of ring sideroblasts and SF3B1 mutation status is critical to diagnosing patients with MDS-RS3,4

≥5% Ring sideroblasts

Assessment of ring sideroblasts for potential MDS-RS diagnosis

Presence of SF3B1

Assessment of ring sideroblasts for potential MDS-RS diagnosis

Assessment of ring sideroblasts for potential MDS-RS diagnosis Potential MDS-RS diagnosis

OR

≥15%Ring sideroblasts

Assessment of ring sideroblasts for potential MDS-RS diagnosis

Assessment of ring sideroblasts for potential MDS-RS diagnosisPotential MDS-RS diagnosis

cDNA=complementary DNA; ddPCR=droplet digital PCR; DNA=deoxyribonucleic acid; NGS=next-generation sequencing; PCR=polymerase chain reaction; TATs=turnaround times.

REBLOZYL is approved for patients with MDS-RS who are failing an ESA and require ≥2 RBC units/8 weeks5

There is currently a degree of variability in how pathologists describe the presence of ring sideroblasts in pathology reports6

  • Ring sideroblasts quantification should be included on the lab report in addition to the assessment of SF3B1 mutation status3,4
  • Quantitative reporting is critical to identifying patients with MDS-RS. REBLOZYL is approved specifically for patients with MDS-RS–associated anemia5
  • Variability in reporting of bone marrow specimens may result in incomplete or misleading information6

There is a strong link between MDS-RS, MDS/MPN-RS-T, and an SF3B1 mutation4

Proportion of patients with an SF3B1 mutation7

Proportion of patients with an SF3B1 mutation Proportion of patients with an SF3B1 mutation

79%

of patients with MDS-RS also have an SF3B1 mutation

The presence of an SF3B1 mutation and RS ≥5% could identify a diagnosis of MDS-RS and indicate the patient may be eligible for REBLOZYL therapy4,5

A range of different technologies can be used by pathologists to test for SF3B1 mutations8-13

ddPCR8,9

  • ddPCR works by partitioning a sample of DNA or cDNA into many individual, parallel PCR reactions
  • This is a relatively new technology that can provide short TATs or laboratories

Real-time PCR9,10

  • Real-time PCR can be used for both qualitative and quantitative assays
  • This method produces faster TATs than other methods of sequencing

Sanger sequencing9,11

  • Sanger sequencing is a well-established but comparably expensive method adopted by laboratories
  • TAT is 1-2 days

NGS9,12,13

  • NGS can analyze numerous genes simultaneously and is the most frequently used technology for SF3B1 testing
  • This is a relatively costly method and generally takes the laboratories ~2-21 days to report

cDNA=complementary DNA; ddPCR=droplet digital PCR; DNA=deoxyribonucleic acid; NGS=next-generation sequencing;
PCR=polymerase chain reaction; TATs=turnaround times.

INDICATIONS

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.

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 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.

Extramedullary Hematopoietic 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%).

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.

Please click here for full Prescribing Information for REBLOZYL.

References: 1. Fenaux P, Haase D, Sanz GF, Santini V, Buske C; ESMO Guidelines Working Group. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3):iii57-iii69. 2. Lee S-H, Erber WN, Porwit A, Tomonaga M, Peterson LC; International Council for Standardization In Hematology. ICSH guidelines for the standardization of bone marrow specimens and reports. Int J Lab Hematol. 2008;30(5):349-364. 3. Kubasch AS, Fenaux P, Platzbecker U. Development of luspatercept to treat ineffective erythropoiesis. Blood Adv. 2021;5(5):1565-1575. 4. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. 5. REBLOZYL [US Prescribing Information]. Summit, NJ: Celgene Corporation; 2022. 6. Sever C, Abbott CL, de Baca ME. Bone marrow synoptic reporting for hematologic neoplasms: guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med. 2016;140(9):932-949. 7. Malcovati L, Papaemmanuil E, Bowen DT, et al. Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. Blood. 2011;118(24):6239-6246. 8. Taylor SC, Laperriere G, Germain H. Droplet digital PCR versus qPCR for gene expression analysis with low abundant targets: from variable nonsense to publication quality data. Scientific Reports. 2017;7(2409):1-8. 9. Sherwood JL, Brown H, Rettino A, et al. Key differences between 13 KRAS mutation detection technologies and their relevance for clinical practice. ESMO Open. 2017;2:1-12. 10. Bio-Rad. What is real-time PCR (qPCR)? Accessed August 15, 2022. https://www.bio-rad.com/en-us/applications-technologies/what-real-time-pcr-qpcr? 11. Heather JM and Chain B. The sequence of sequencers: The history of sequencing DNA. Genomics. 2016;107:1-8. 12. Aguilera-Diaz A, Vazquez I, Ariceta B, et al. Assessment of the clinical utility of four NGS panels in myeloid malignancies. Suggestions for NGS panel choice or design. PLoS ONE. 2020;15(1):1-24. 13. Spaulding TP, Stockton SS, Savona MR. The evolving role of next generation sequencing in myelodysplastic syndromes. Br J Haematol. 2020;188(2):224-239.

Bristol Myers SquibbTM logo
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.

© 2022 Bristol-Myers Squibb Company.
2007-US-2200263 12/2022

References: 1. Fenaux P, Haase D, Sanz GF, Santini V, Buske C; ESMO Guidelines Working Group. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3):iii57-iii69. 2. Lee S-H, Erber WN, Porwit A, Tomonaga M, Peterson LC; International Council for Standardization In Hematology. ICSH guidelines for the standardization of bone marrow specimens and reports. Int J Lab Hematol. 2008;30(5):349-364. 3. Kubasch AS, Fenaux P, Platzbecker U. Development of luspatercept to treat ineffective erythropoiesis. Blood Adv. 2021;5(5):1565-1575. 4. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. 5. REBLOZYL [US Prescribing Information]. Summit, NJ: Celgene Corporation; 2022. 6. Sever C, Abbott CL, de Baca ME. Bone marrow synoptic reporting for hematologic neoplasms: guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med. 2016;140(9):932-949. 7. Malcovati L, Papaemmanuil E, Bowen DT, et al. Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. Blood. 2011;118(24):6239-6246. 8. Taylor SC, Laperriere G, Germain H. Droplet digital PCR versus qPCR for gene expression analysis with low abundant targets: from variable nonsense to publication quality data. Scientific Reports. 2017;7(2409):1-8. 9. Sherwood JL, Brown H, Rettino A, et al. Key differences between 13 KRAS mutation detection technologies and their relevance for clinical practice. ESMO Open. 2017;2:1-12. 10. Bio-Rad. What is real-time PCR (qPCR)? Accessed August 15, 2022. https://www.bio-rad.com/en-us/applications-technologies/what-real-time-pcr-qpcr? 11. Heather JM and Chain B. The sequence of sequencers: The history of sequencing DNA. Genomics. 2016;107:1-8. 12. Aguilera-Diaz A, Vazquez I, Ariceta B, et al. Assessment of the clinical utility of four NGS panels in myeloid malignancies. Suggestions for NGS panel choice or design. PLoS ONE. 2020;15(1):1-24. 13. Spaulding TP, Stockton SS, Savona MR. The evolving role of next generation sequencing in myelodysplastic syndromes. Br J Haematol. 2020;188(2):224-239.