Active Ingredient: Luspatercept
Luspatercept is indicated in adults for the treatment of transfusion-dependent anaemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS).
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 1.75 milligrams luspatercept per kilogram of body weight, once every 3 weeks.
The recommended starting dose of luspatercept is 1 mg/kg administered once every 3 weeks.
The recommended desired Hb concentration range is between 10 g/dL and 12 g/dL. Dose increase for insufficient response is provided below.
Table 1. Dose increase for insufficient response:
| Dose at 1 mg/kg | Dose increase |
| If after at least 2 consecutive doses at 1 mg/kg, a patient: • is not RBC transfusion-free, or • does not reach Hb concentration of ≥ 10 g/dL and the Hb increase is < 1 g/dL | • Dose should be increased to 1.33 mg/kg |
| Dose at 1.33 mg/kg | Dose increase |
| If after at least 2 consecutive doses at 1.33 mg/kg, a patient: • is not RBC transfusion-free, or • does not reach Hb concentration of ≥ 10 g/dL and the Hb increase is < 1 g/dL | • 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 (see Table 2).
Increase to next dose level based on current dose is provided below.
Table 2. Increase to next dose level for MDS:
| Current dose | Increased dose |
| 0.8 mg/kg | 1 mg/kg |
| 1 mg/kg | 1.33 mg/kg |
| 1.33 mg/kg | 1.75 mg/kg |
In case of Hb increase > 2 g/dL within 3 weeks in absence of transfusion compared with the Hb value at previous dose, luspatercept 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 0.8 mg/kg.
Reduced dose during treatment with luspatercept are provided below.
Table 3. Reduced dose for MDS:
| Current dose | Reduced dose |
| 1.75 mg/kg | 1.33 mg/kg |
| 1.33 mg/kg | 1 mg/kg |
| 1 mg/kg | 0.8 mg/kg |
Instructions on dose interruptions or reductions for luspatercept treatment-related adverse reactions are outlined in Table 4.
Table 4. 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 for the respective indication being treated (see Table 2.
Luspatercept should be discontinued if patients do not experience a decrease in transfusion burden including no increase from baseline Hb 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.
Luspatercept solution should be injected subcutaneously into the upper arm, thigh or abdomen.
Liability Disclaimer : RxReasoner has utilized reasonable care in providing content and services that are accurate, complete and up to date. However, RxReasoner does not accept any responsibility or liability about it. The content and services of RxReasoner are for informational purposes only and they are not intended to be a substitute for the knowledge, expertise, skill, and judgment of physicians, pharmacists, nurses, or other healthcare professionals involved in patient care. RxReasoner offers no medical advice. Users are responsible for the use of the provided content. A shown indication or treatment should not be construed to indicate that the medication is safe, appropriate, or effective in any given patient or under any particular circumstances. The absence of an indication or treatment should not roule out the existence of other appropriate medications. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition or medicament. RxReasoner is not liable for any damages allegedly sustained arising out of the use of its content and services.