Active Ingredient: Luspatercept
Luspatercept is indicated in adults for the treatment of anaemia associated with transfusion-dependent and non-transfusion-dependent beta-thalassaemia.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Subcutaneous, 1 milligrams luspatercept per kilogram of body weight, once every 3 weeks. Afterwards, subcutaneous, between 1 milligrams luspatercept per kilogram of body weight and 1.25 milligrams luspatercept per kilogram of body weight, once every 3 weeks.
The recommended starting dose of Reblozyl is 1 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 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 (see Table 1).
In patients who do not achieve or maintain a response, defined as an increase from baseline in pre-dose Hb of ≥ 1 g/dL, after ≥ 2 consecutive doses (6 weeks) at the same dose level (in absence of transfusions, i.e. at least 3 weeks after the last transfusion), the dose should be increased by one dose level (see Table 1). The dose should not exceed the maximum dose of 1.25 mg/kg every 3 weeks.
Increase to next dose level based on current dose is provided below.
Table 1. Increase to next dose level for β-thalassaemia:
| Current dose | Increased dose |
| 0.6 mg/kg* | 0.8 mg/kg |
| 0.8 mg/kg | 1 mg/kg |
| 1 mg/kg | 1.25 mg/kg |
* Applicable only to non-transfusion-dependent β-thalassaemia.
In case of Hb increase > 2 g/dL within 3 weeks in absence of transfusion compared with the Hb value at previous dose, Reblozyl dose should be reduced by one dose level.
If the Hb is ≥ 12 g/dL in the absence of transfusion for at least 3 weeks, the dose should be delayed until the Hb is ≤ 11 g/dL. If there is also a concomitant rapid increase in Hb from the Hb value at previous dose (> 2 g/dL within 3 weeks in absence of transfusion), a dose reduction to one step down should be considered after the dose delay.
Dose should not be reduced below 0.6 mg/kg.
Reduced dose during treatment with luspatercept are provided below.
Table 2. Reduced dose for β-thalassaemia:
| Current dose | Reduced dose |
| 1.25 mg/kg | 1 mg/kg |
| 1 mg/kg | 0.8 mg/kg |
| 0.8 mg/kg | 0.6 mg/kg* |
* Applicable only to non-transfusion-dependent β-thalassaemia.
Instructions on dose interruptions or reductions for luspatercept treatment-related adverse reactions are outlined in Table 3.
Table 3. Dose modification instructions:
| Treatment-related adverse reactions* | Dose instructions |
| Grade 2 adverse reactions, including Grade 2 hypertension | • Interrupt treatment • Restart at previous dose when adverse reaction has improved or returned to baseline |
| Grade ≥ 3 hypertension | • Interrupt treatment • Restart at reduced dose once the blood pressure is controlled as per dose reduction guidance |
| Other persistent Grade ≥ 3 adverse reactions | • Interrupt treatment • Restart at previous dose or at reduced dose when adverse reaction has improved or returned to baseline as per dose reduction guidance |
| Extramedullary haemopoiesis (EMH) masses causing serious complications | • Discontinue treatment |
* Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: life-threatening.
In case of a missed or delayed scheduled treatment administration, the patient should be administered luspatercept as soon as possible and dosing continued as prescribed with at least 3 weeks between doses.
If patients experience a loss of response to luspatercept, 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 (see Table 1).
Luspatercept should be discontinued if patients do not experience a reduction in transfusion burden (for transfusion-dependent β-thalassaemia patients), or an increase from baseline Hb in the absence of transfusions (for non-transfusion-dependent β-thalassaemia patients) 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 luspatercept. Limited data are available in β-thalassaemia patients ≥60 years of age.
Luspatercept solution should be injected subcutaneously into the upper arm, thigh or abdomen.
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