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Warnings and precautions1

Thrombosis/Thromboembolism

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

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 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.

Adverse reactions with REBLOZYL1

  • The median time on treatment with REBLOZYL was 50.4 weeks (range, 3–221 weeks); 67% of patients were exposed for 6 months or longer and 49% were exposed for >1 year
  • Among the 242 patients treated with REBLOZYL, 5 (2.1%) had a fatal adverse reaction
  • The most common (≥2%) Grade ≥3 adverse reactions included fatigue, hypertension, syncope, and musculoskeletal pain
  • Selected laboratory abnormalities that changed from Grade 0–1 at baseline to Grade ≥2 at any time during the studies in at least 10% of patients included creatinine clearance decreased, total bilirubin increased, and alanine aminotransferase increased
  • Other clinically relevant adverse reactions reported in <5% of patients included bronchitis, urinary tract infection, and hypertension

The majority of adverse reactions with REBLOZYL were Grade 1 or 2 (mild to moderate)1

Adverse reactions (≥5%) in patients receiving REBLOZYL with a difference between arms of >2% in MEDALIST trial through cycle 81

Body system/adverse reaction REBLOZYL
(n = 153)
Placebo
(n = 76)
All Grades
n (%)
Grade 3
n (%)
All Grades
n (%)
Grade 3
n (%)
General disorders and administration site conditions
Fatiguea,b 63 (41) 11 (7) 17 (22) 2 (3)
Musculoskeletal and connective tissue disorders
Musculoskeletal painb 30 (20) 3 (2) 11 (14) 0 (0)
Nervous system disorders
Dizziness/vertigo 28 (18) 1 (<1) 5 (7) 1 (1)
Headacheb 21 (14) 0 (0) 5 (7) 0 (0)
Syncope/presyncope 8 (5) 5 (3) 0 (0) 0 (0)
Gastrointestinal disorders
Nauseab 25 (16) 1 (<1) 8 (11) 0 (0)
Diarrheab 25 (16) 0 (0) 7 (9) 0 (0)
Respiratory, thoracic, and mediastinal disorders
Dyspneab 20 (13) 2 (1) 4 (5) 1 (1)
Immune system disorders
Hypersensitivity reactionsb 15 (10) 1 (<1) 5 (7) 0 (0)
Renal and urinary disorders
Renal impairmentb 12 (8) 3 (2) 3 (4) 0 (0)
Cardiac disorders
Tachycardiab 12 (8) 0 (0) 1 (1) 0 (0)
Injury poisoning and procedural complications
Injection site reactions 10 (7) 0 (0) 3 (4) 0 (0)
Infections and infestations
Upper respiratory tract infection 10 (7) 1 (<1) 2 (3) 0 (0)
Influenza/influenza-like illness 9 (6) 0 (0) 2 (3) 0 (0)

a Includes asthenic conditions.

b Reaction includes similar/grouped terms.

Selected Grades 2 to 4 treatment-emergent laboratory abnormalities through cycle 8 in the MEDALIST trial1

Parameter REBLOZYL Placebo
Na n (%) Na n (%)
ALT elevated 151 13 (9) 74 5 (7)
AST elevated 152 6 (4) 76 0 (0)
Total bilirubin elevated 140 17 (12) 66 3 (5)
Creatinine clearance reduced 113 30 (27) 62 13 (21)

aNumber of patients at Grades 0 to 1 at baseline.

ALT, alanine aminotransferase; AST, aspartate aminotransferase.

Immunogenicity1

  • Of 260 patients with MDS who were treated with REBLOZYL and evaluable for the presence of anti-luspatercept-aamt antibodies, 23 patients (8.9%) tested positive for treatment-emergent anti-luspatercept-aamt antibodies, including 9 patients (3.5%) who had neutralizing antibodies
  • Luspatercept-aamt serum concentration tended to decrease in the presence of neutralizing antibodies
  • There were no severe acute systemic hypersensitivity reactions reported for patients with anti-luspatercept-aamt antibodies in REBLOZYL clinical trials, and there was no association between hypersensitivity type reaction or injection site reaction and presence of anti-luspatercept-aamt antibodies

Lactation1

  • 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. There are no data on the presence of REBLOZYL in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with REBLOZYL, and for 3 months after the last dose

REBLOZYL discontinuations and dose modifications in the safety population1

  • The safety of REBLOZYL at the recommended dose and schedule was evaluated in 242 patients with MDS-RS (n = 192) or other myeloid neoplasms (n = 50)

Discontinuations due to adverse reactions1

  • 4.5% (11/242) of patients who received REBLOZYL discontinued treatment due to an adverse reaction

Dose reductions due to adverse reactions1

  • 2.9% (7/242) of patients who received REBLOZYL required a dose reduction due to an adverse reaction

Additional analysis of treatment-emergent adverse events (TEAEs) by REBLOZYL treatment cycle2

TEAEs ≥5% incidence by treatment cycle

*Includes week 25 assessment.

Analysis limitations

  • All patients in both arms were eligible to receive BSC, including RBC transfusions as needed1
  • Adverse events (AEs) with a duration overlapping multiple cycles were only counted in the first overlapped cycle. If an AE occurred multiple times in different cycles, it was counted once in each cycle. If an AE occurred multiple times within the same cycle, it was counted only once. If a patient experienced multiple events under the same MedDRA 20.0 preferred term, then the patient was counted only once for the preferred term2
  • Patients who met the criteria and remained on double-blind treatment after completion of week 25 assessment may have continued dosing in the extension phase of the treatment period until the subject experienced unacceptable toxicities, disease progression, withdrew consent, or met any other discontinuation criteria1,2
  • Fatigue TEAE does not include broader asthenic conditions adverse drug reactions (ADRs)

Additional analysis information

  • Analysis is based on data through week 483
  • The chart displays TEAEs independent of attribution of treatment or disease. The percentage shown in this graph does not match the Adverse Reactions table above
  • TEAEs are undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment
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Indication

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%) 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.

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. REBLOZYL [Prescribing Information]. Summit, NJ: Celgene Corporation; 2020. 2. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382(2 suppl):140-151. 3. Data on file. Celgene Corporation. Summit, New Jersey.