Source: European Medicines Agency (EU) Revision Year: 2020
Reblozyl is indicated for the treatment of adult patients with transfusion-dependent anaemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts, who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy (see section 5.1).
Reblozyl is indicated for the treatment of adult patients with transfusion-dependent anaemia associated with beta-thalassaemia (see section 5.1).
Reblozyl treatment should be initiated by a physician experienced in treatment of haematological diseases.
Prior to each Reblozyl administration, the haemoglobin (Hb) level of patients should be assessed. In case of a red blood cell (RBC) transfusion occurring prior to dosing, the pre-transfusion Hb level must be considered for dosing purposes.
The recommended starting dose of Reblozyl is 1.0 mg/kg administered once every 3 weeks.
In patients who are not RBC transfusion-free after at least 2 consecutive doses at the 1.0 mg/kg starting dose, the dose should be increased to 1.33 mg/kg. If patients are not RBC transfusion-free after at least 2 consecutive doses at the 1.33 mg/kg dose level, the dose should be increased to 1.75 mg/kg. The dose increase should not occur more frequently than every 6 weeks (2 administrations) and should not exceed the maximum dose of 1.75 mg/kg every 3 weeks. The dose should not be increased immediately after a dose delay. For patients with a pre-dose Hb level of >9 g/dL and who have not yet achieved transfusion independence, a dose increase may be required at the physician’s discretion; the risk of Hb increasing above the target threshold with concomitant transfusion cannot be excluded.
If a patient loses response (i.e., transfusion independence), the dose should be increased by one dose level.
The recommended starting dose of Reblozyl is 1.0 mg/kg administered once every 3 weeks.
In patients who do not achieve a response, defined as a reduction in RBC transfusion burden of at least a third after ≥2 consecutive doses (6 weeks), at the 1.0 mg/kg starting dose, the dose should be increased to 1.25 mg/kg. The dose should not be increased beyond the maximum dose of 1.25 mg/kg every 3 weeks.
If a patient loses response (if the RBC transfusion burden increases again after an initial response) the dose should be increased by one dose level.
In case of Hb increase >2 g/dL within 3 weeks of luspatercept treatment in absence of transfusion, the Reblozyl dose should be reduced by one dose level.
If the Hb is ≥11.5 g/dL in the absence of transfusion for at least 3 weeks, the dose should be delayed until the Hb is ≤11.0 g/dL. If there is also a concomitant rapid increase in Hb (>2 g/dL within 3 weeks in absence of transfusion), a dose reduction to one step down (minimum 0.8 mg/kg) should be considered after the dose delay.
Dose should not be reduced below 0.8 mg/kg.
Dose reductions during treatment with luspatercept are provided below
Table 1. Dose reductions for MDS:
| Current dose | Dose reduction |
|---|---|
| 1.75 mg/kg | 1.33 mg/kg |
| 1.33 mg/kg | 1 mg/kg |
| 1 mg/kg | 0.8 mg/kg |
Table 2. Dose reductions for β-thalassaemia:
| Current dose | Dose reduction |
|---|---|
| 1.25 mg/kg | 1 mg/kg |
| 1 mg/kg | 0.8 mg/kg |
If patients experience persistent treatment-related Grade 3 or higher adverse reactions (see section 4.8), the treatment should be delayed until toxicity has improved or returned to baseline.
After a dose delay, patients should be re-started at their previous dose or at reduced dose as per dose reduction guidance.
In case of a missed or delayed scheduled treatment administration, the patient should be administered Reblozyl as soon as possible and dosing continued as prescribed with at least 3 weeks between doses.
If patients experience a loss of response to Reblozyl, causative factors (e.g. a bleeding event) should be assessed. If typical causes for a loss of haematological response are excluded, dose increase should be considered as described above for the respective indication being treated.
Reblozyl should be discontinued if patients do not experience a reduction in transfusion burden after 9 weeks of treatment (3 doses) at the maximum dose level if no alternative explanations for response failure are found (e.g. bleeding, surgery, other concomitant illnesses) or if unacceptable toxicity occurs at any time.
No starting dose adjustment is required for Reblozyl (see section 5.2).
No starting dose adjustment is required for patients with total bilirubin (BIL) >upper limit of normal (ULN) and/or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <3 x ULN (see section 5.2). No specific dose recommendation can be made for patients with ALT or AST ≥3 x ULN or liver injury CTCAE Grade ≥3 due to lack of data (see section 5.2).
No starting dose adjustment is required for patients with mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] <90 and ≥30 mL/min/1.73 m²). No specific dose recommendation can be made for patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) due to lack of clinical data (see section 5.2). Patients with renal impairment at baseline should be closely monitored for renal function as per standard of care.
There is no relevant use of Reblozyl in the paediatric population for the indication of myelodysplastic syndromes, or in paediatric patients less than 6 months of age in β-thalassaemia. For non-clinical data, see section 5.3.
The safety and efficacy of Reblozyl in the paediatric patients aged from 6 months to less than 18 years have not yet been established in β-thalassaemia. For non-clinical data, see section 5.3.
For subcutaneous use.
After reconstitution, Reblozyl solution should be injected subcutaneously into the upper arm, thigh or abdomen. The exact total dosing volume of the reconstituted solution required for the patient should be calculated and slowly withdrawn from the single-dose vial(s) into a syringe.
The recommended maximum volume of medicinal product per injection site is 1.2 mL. If more than 1.2 mL is required, the total volume should be divided into separate similar volume injections and administered across separate sites.
If multiple injections are required, a new syringe and needle must be used for each subcutaneous injection. No more than one dose from a vial should be administered.
If the Reblozyl solution has been refrigerated after reconstitution, it should be removed from the refrigerator 15-30 minutes prior to injection to allow it to reach room temperature. This will allow for a more comfortable injection.
For instructions on reconstitution of the medicinal product before administration, see section 6.6.
Overdose with luspatercept may cause an increase of Hb values above the desired level. In the event of an overdose, treatment with luspatercept should be delayed until Hb is ≤11 g/dL.
Unopened vial: 3 years.
After reconstitution:
When stored in the original container, chemical and physical in-use stability of the reconstituted medicinal product has been demonstrated for up to 8 hours at room temperature (≤25°C) or for up to 24 hours at 2°C-8°C.
From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2°C-8°C.
Do not freeze the reconstituted solution.
Store in a refrigerator (2°C-8°C).
Do not freeze.
Store in the original carton in order to protect from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
Reblozyl 25 mg powder for solution for injection: 3 mL Type I glass vial with a hydrophobic inner coating closed with a bromobutyl rubber stopper and aluminium seal with yellow polypropylene flip-off cap.
Reblozyl 75 mg powder for solution for injection: 3 mL Type I glass vial with a hydrophobic inner coating closed with a bromobutyl rubber stopper and aluminium seal with orange polypropylene flip-off cap.
Pack size: 1 vial.
Reblozyl must be reconstituted gently prior to administration. Aggressive shaking should be avoided.
Reblozyl is supplied as a lyophilised powder for reconstitution before use. Only water for injections (WFI) should be used when reconstituting Reblozyl.
The appropriate number of Reblozyl vials should be reconstituted to achieve the desired dose. A syringe with appropriate graduations must be used for reconstitution to ensure accurate dosage.
The following steps should be followed for reconstitution:
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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