SAFETY

Safety Profile

The safety evaluation of Reblozyl in β-thalassemia is based on the double-blind, randomized, placebo-controlled Phase 3 BELIEVE trial (with 224 patients treated with Reblozyl and 112 patients receiving placebo).

The most commonly reported Grade 3 or higher adverse drug reaction was hyperuricemia. The most serious adverse reactions reported included thromboembolic events of deep vein thrombosis, ischemic stroke, portal vein thrombosis, and pulmonary embolism.1

Most frequently reported adverse drug reactions
in at least 15% of patients receiving Reblozyl1

Headache

Bone Pain Was Reported in 2.6% Patients Receiving Reblozyl (3.9% Placebo)

Bone pain

Arthralgia Was Reported In 5.2% Patients Receiving Reblozyl (11.8% Placebo)

Arthralgia

Bone pain, asthenia, fatigue, dizziness, and headache occurred more frequently during the first 3 months1

The frequency for each adverse reaction observed in the BELIEVE trial is shown in the center table.

ADVERSE DRUG REACTIONS IN PATIENTS TREATED
WITH REBLOZYL FOR β-THALASSEMIA1
SYSTEM ORGAN CLASS PREFERRED TERM FREQUENCY (ALL GRADES)a
Infections and infestations Bronchitis Common
Urinary tract infection Common
Upper respiratory
tract infection
Very common
Influenza Common
Immune system disorders Hypersensitivityb Common
Metabolism and nutrition disorders Hyperuricemia Common
Nervous system disorders Dizziness Very common
Headache Very common
Syncope/presyncope Common
Ear and labyrinth disorders Vertigo/vertigo positional Common
Vascular disorders Hypertensionc Common
Thromboembolic eventsd Common
Respiratory, thoracic
and mediastinal disorders
Dyspnea Common
Gastrointestinal disorders Diarrhoea Very common
Nausea Common
Musculoskeletal and
connective tissue
disorders
Back pain Very common
Arthralgia Very common
Bone pain Very common
General disorders and
administration site
conditions
Fatigue Very common
Asthenia Common
Injection site reactionse Common

aFrequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000).1

bHypersensitivity includes eyelid edema, drug hypersensitivity, swelling face, periorbital edema, face edema, angioedema, lip swelling, and drug eruption.1

cHypertension reaction includes essential hypertension, hypertension, and hypertensive crisis.1

dThromboembolic events include deep vein thrombosis, portal vein thrombosis, ischemic stroke, and pulmonary embolism.1

eInjection site reactions include injection site erythema, injection site pruritus, injection site swelling, and injection site rash.1

Safety Profile

The safety evaluation of Reblozyl in β-thalassemia is based on the double-blind, randomized, placebo-controlled Phase 3 BELIEVE trial (with 224 patients treated with Reblozyl and 112 patients receiving placebo).

Most frequently reported adverse drug reactions in at least 15% of patients receiving Reblozyl1

Headache

Bone Pain Was Reported in 2.6% Patients Receiving Reblozyl (3.9% Placebo)

Bone pain

Arthralgia Was Reported In 5.2% Patients Receiving Reblozyl (11.8% Placebo)

Arthralgia

Bone pain, asthenia, fatigue, dizziness, and headache occurred less frequently after the first 3 months

The most commonly reported Grade 3 or higher adverse drug reaction was hyperuricemia The most serious adverse reactions reported included thromboembolic events of deep vein thrombosis, ischemic stroke, portal vein thrombosis, and pulmonary embolism.1

ADVERSE DRUG REACTIONS OBSERVED/REPORTED IN PATIENTS TREATED WITH REBLOZYL1
SYSTEM ORGAN CLASS
PREFERRED TERM
FREQUENCY (ALL GRADES)a
Infections and infestations
Bronchitis Common
Urinary tract infection Common
Upper respiratory tract infection Very common
Influenza Common
Immune system disorders
Hypersensitivityb Common
Metabolism and nutrition disorders
Hyperuricemia Common
Nervous system disorders
Dizziness Very common
Headache Very common
Syncope/presyncope Common
Ear and labyrinth disorders
Vertigo/vertigo positional Common
Vascular disorders
Hypertensionc Common
Thromboembolic eventsd Common
Respiratory, thoracic and mediastinal disorders
Dyspnea Common
Gastrointestinal disorders
Diarrhea Very common
Nausea Common
Musculoskeletal and connective tissue disorders
Back pain Very common
Arthralgia Very common
Bone pain Very common
General disorders and administration site conditions
Fatigue Very common
Asthenia Common
Injection site reactionse Common

a Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000).1

bHypersensitivity includes eyelid edema, drug hypersensitivity, swelling face, periorbital edema, face edema, angioedema, lip swelling, and drug eruption.1

cHypertension reaction includes essential hypertension, hypertension, and hypertensive crisis.1

d Thromboembolic events include deep vein thrombosis, portal vein thrombosis, ischemic stroke, and pulmonary embolism.1

eInjection site reactions include injection site erythema, injection site pruritus, injection site swelling, and injection site rash.1

Reference:

1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020.

Selected Adverse Reactions

Selected adverse reactions across MEDALIST and BELIEVE trials1
  • Bone pain: Bone pain was reported in 19.7% of patients with β-thalassemia treated with Reblozyl (placebo 8.3%) and in 2.6% of patients with MDS treated with Reblozyl (placebo 3.9%). In patients with β-thalassemia treated with Reblozyl, bone pain was most common in the first 3 months (16.6%) compared to months 4-6 (3.7%). Most events (41/44 events) were Grade 1-2, with 3 events Grade 3. One of the 44 events was serious, and 1 event led to treatment discontinuation.1
  • Arthralgia: Arthralgia was reported in 19.3% of patients with β-thalassemia treated with Reblozyl (placebo 11.9%) and in 5.2% of patients with MDS treated with Reblozyl (placebo 11.8%). In the patients with β-thalassemia treated with Reblozyl, arthralgia led to treatment discontinuation in 2 patients (0.9%).1
  • Hypertension: Patients treated with Reblozyl had an average increase in systolic and diastolic blood pressure of 5 mm Hg from baseline not observed in patients receiving placebo. Hypertension was reported in 8.5% of patients with MDS (placebo 9.2%) and in 8.1% of patients with β-thalassemia (placebo 2.8%).1
    • In patients with MDS, Grade 3 events were reported for 5 patients (3.3%) treated with Reblozyl and in 3 patients (3.9%) receiving placebo. No patient discontinued due to hypertension.1
    • In patients with β-thalassemia, Grade 3 events were reported in 4 patients (1.8%) treated with Reblozyl (0.0% placebo). No patient discontinued due to hypertension1
  • Hypersensitivity: Hypersensitivity-type reactions (including eyelid edema, drug hypersensitivity, swelling face, periorbital edema, face edema, angioedema, lip swelling, drug eruption) were reported in 4.6% of patients with MDS (2.6% placebo) and 4.5% of patients with β-thalassemia treated with Reblozyl (1.8% placebo). In clinical studies, all events were Grade 1/2. In patients with β-thalassemia treated with Reblozyl, hypersensitivity led to treatment discontinuation in 1 patient (0.4%).1
  • Thromboembolic events (TEEs): Thromboembolic events (including deep vein thrombosis, portal vein thrombosis, ischemic stroke, and pulmonary embolism) occurred in 3.6% of patients with β-thalassemia receiving Reblozyl (placebo 0.9%). All events were reported in patients who had undergone splenectomy and had at least 1 other risk factor. No difference in TEEs was observed between Reblozyl and placebo arms in MDS patients.1
  • Injection site reactions: Injection site reactions (including injection site erythema, injection site pruritus, injection site swelling, and injection site rash) were reported in 3.9% of patients with MDS (placebo 0.0%) and in 2.2% of patients with β-thalassemia receiving Reblozyl (placebo 1.8%). In clinical studies, all events were Grade 1 and none led to discontinuation.1
  • Immunogenicity: In clinical studies of MDS, an analysis of 260 patients who were treated with Reblozyl and who were evaluable for the presence of anti-luspatercept antibodies, 23 (8.8%) patients tested positive for treatment‑emergent anti-luspatercept antibodies, including 9 (3.5%) patients who had neutralizing antibodies against Reblozyl.1

    In clinical studies of β-thalassemia, an analysis of 284 patients who were treated with Reblozyl and who were evaluable for the presence of anti-luspatercept antibodies, 4 (1.4%) of patients tested positive for treatment-emergent anti-luspatercept antibodies, including 2 (0.7%) of patients who had neutralizing antibodies against Reblozyl.1
  • Luspatercept serum concentration tended to decrease in the presence of neutralizing antibodies. There were no severe systemic hypersensitivity reactions reported for patients with anti-luspatercept antibodies. There was no association between hypersensitivity type reactions or injection site reactions and presence of anti-luspatercept antibodies.1

Selected adverse reactions in β-thalassemia1

Bone Pain Was Reported in 2.6% Patients Receiving Reblozyl (3.9% Placebo)

Bone Pain

19.7% Reblozyl

8.3% Placebo

Arthralgia Was Reported In 5.2% Patients Receiving Reblozyl (11.8% Placebo)

Arthralgia

19.3% Reblozyl

11.9% Placebo

Hypertension Was Reported in 8.5% Patients Receiving Reblozyl (9.2% Placebo)

Hypertension

8.1% Reblozyl

2.8% Placebo

Hypersensitivity

4.5% Reblozyl

1.8% Placebo

Thromboembolic Events

3.6% Reblozyl

0.9% Placebo

Injection Site Reactions Were Reported In 3.9% Of Patients Receiving Reblozyl (0% Placebo)

Injection Site Reactions

2.2% Reblozyl

1.8% Placebo

8.8% Of Patients Receiving Reblozyl Tested Positive For Treatment-Emergent Anti-Reblozyl Antibodies

Immunogenicity

1.4% Reblozyl patients tested positive for treatment-emergent anti-luspatercept antibodies

Selected Adverse Reactions

Selected adverse reactions across MEDALIST and BELIEVE trials1

Bone Pain Was Reported in 2.6% Patients Receiving Reblozyl (3.9% Placebo)

Bone Pain

19.7% Reblozyl

8.3% Placebo

Bone pain: Bone pain was reported in 19.7% of patients with β-thalassemia treated with Reblozyl (placebo 8.3%) and in 2.6% of patients with MDS treated with Reblozyl (placebo 3.9%). In patients with β-thalassemia treated with Reblozyl, bone pain was most common in the first 3 months (16.6%) compared to months 4-6 (3.7%). Most events (41/44 events) were Grade 1-2, with 3 events Grade 3. One of the 44 events was serious, and 1 event led to treatment discontinuation.1

Arthralgia Was Reported In 5.2% Patients Receiving Reblozyl (11.8% Placebo)

Arthralgia

19.3% Reblozyl

11.9% Placebo

Arthralgia: Arthralgia was reported in 19.3% of patients with ß-thalassemia treated with Reblozyl (placebo 11.9%) and in 5.2% of patients with MDS treated with Reblozyl (placebo 11.8%). In the patients with β-thalassemia treated with Reblozyl, arthralgia led to treatment discontinuation in 2 patients (0.9%).1

Hypertension Was Reported in 8.5% Patients Receiving Reblozyl (9.2% Placebo)

Hypertension

8.1% Reblozyl

2.8% Placebo

Hypertension: Patients treated with Reblozyl had an average increase in systolic and diastolic blood pressure of 5 mm Hg from baseline not observed in patients receiving placebo. Hypertension was reported in 8.5% of patients with MDS (placebo 9.2%) and in 8.1% of patients with β-thalassemia (placebo 2.8%).1

  • In patients with MDS, Grade 3 events were reported for 5 patients (3.3%) treated with Reblozyl and in 3 patients (3.9%) receiving placebo. No patient discontinued due to hypertension.1
  • In patients with β-thalassemia, Grade 3 events were reported in 4 patients (1.8%) treated with Reblozyl (0.0% placebo). No patient discontinued due to hypertension1

Hypersensitivity

4.5% Reblozyl

1.8% Placebo

Hypersensitivity: Hypersensitivity-type reactions (including eyelid edema, drug hypersensitivity, swelling face, periorbital edema, face edema, angioedema, lip swelling, drug eruption) were reported in 4.6% of patients with MDS (2.6% placebo) and 4.5% of patients with β-thalassemia treated with Reblozyl (1.8% placebo). In clinical studies, all events were Grade 1/2. In patients with β-thalassemia treated with Reblozyl, hypersensitivity led to treatment discontinuation in 1 patient (0.4%).1

Thromboembolic events (TEEs)

3.6% Reblozyl

0.9% Placebo

Thromboembolic events (including deep vein thrombosis, portal vein thrombosis, ischemic stroke, and pulmonary embolism) occurred in 3.6% of patients with β-thalassemia receiving Reblozyl (placebo 0.9%). All events were reported in patients who had undergone splenectomy and had at least 1 other risk factor. No difference in TEEs was observed between Reblozyl and placebo arms in MDS patients.1

Injection Site Reactions Were Reported In 3.9% Of Patients Receiving Reblozyl (0% Placebo)

Injection site reactions

2.2% Reblozyl

1.8% Placebo

Injection site reactions: Injection site reactions (including injection site erythema, injection site pruritus, injection site swelling, and injection site rash) were reported in 3.9% of patients with MDS (placebo 0.0%) and in 2.2% of patients with β-thalassemia receiving Reblozyl (placebo 1.8%). In clinical studies, all events were Grade 1 and none led to discontinuation.1

8.8% Of Patients Receiving Reblozyl Tested Positive For Treatment-Emergent Anti-Reblozyl Antibodies

Immunogenicity

1.4% of Reblozyl patients
tested positive for
treatment-emergent
anti-luspatercept antibodies

In clinical studies of MDS, an analysis of 260 patients who were treated with Reblozyl and who were evaluable for the presence of anti-luspatercept antibodies, 23 (8.8%) patients tested positive for treatment‑emergent anti-luspatercept antibodies, including 9 (3.5%) patients who had neutralizing antibodies against Reblozyl.1

In clinical studies of β-thalassemia, an analysis of 284 patients who were treated with Reblozyl and who were evaluable for the presence of anti-luspatercept antibodies, 4 (1.4%) of patients tested positive for treatment-emergent anti-luspatercept antibodies, including 2 (0.7%) of patients who had neutralizing antibodies against Reblozyl.1

  • Luspatercept serum concentration tended to decrease in the presence of neutralizing antibodies. There were no severe systemic hypersensitivity reactions reported for patients with anti-luspatercept antibodies. There was no association between hypersensitivity type reactions or injection site reactions and presence of anti-luspatercept antibodies.1

Reference:

1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020.

Discontinuations

Treatment discontinuation due to an adverse event occurred in 2.6% of β-thalassemia patients treated with Reblozyl, and in 2% of MDS patients. Adverse reactions leading to study drug discontinuation in the Reblozyl treatment arm were arthralgia, back pain, bone
pain, and headache.1

Only 2.6% Of ß-Thalassemia Patients Treated With Reblozyl Discontinued Treatment Due To An Adverse Event

Discontinuations

Only 2% Of Patients With MDS Receiving Reblozyl Discontinued Treatment Due To An Adverse Event
of β-thalassemia patients treated with Reblozyl discontinued treatment due to an adverse reaction1

Adverse reactions leading to study drug discontinuation in the Reblozyl treatment arm were arthralgia, back pain, bone pain, and headache.1

Reference:

1. Reblozyl® (luspatercept) Summary of Product Characteristics (SmPC). Celgene 2020.

 

This site is not intended for US or UK healthcare professionals.

The product has received European Medicines Agency approval. The registration status and approved product labels of Reblozyl may vary from country to country. The information on this website is not country-specific and may not be applicable to your country. For more information, please refer to your local Prescribing Information.
IMPORTANT: The information on this website is based on the European Summary of Product Characteristics (EU SmPC).
This site is not intended for US or UK healthcare professionals. View the US site.
The information provided on this website is intended for use by a healthcare professional qualified to prescribe and supply medications, thus requiring specific scientific knowledge and training to interpret it correctly.
I am a European Healthcare Professional (UK excluded)
I am NOT a European Healthcare Professional
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See Section 4.8 in the EU Summary of Product Characteristics for more information. Before prescribing Reblozyl, please refer to the
EU Summary of Product Characteristics.