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luspatercept
Luspatercept is a recombinant fusion protein that targets select endogenous TGF-β superfamily ligands, resulting in Smad2/3 signaling inhibition. Luspatercept is an erythroid maturation agent which promotes late-stage erythroblast differentiation.
Absorption of luspatercept was not significantly affected by the site of subcutaneous injection.
| T max |
7 days (median) |
| Time to reach steady state |
After 3 doses (given q3 weeks) |
Catabolized into amino acids by general protein degradation in multiple tissues.
| Half-life |
13 days (in patients with MDS) |
- Transfusion-dependent anemia from myelodysplastic syndromes (MDS)
Refer to the product monograph for a full list and details of approved indications.
Emetogenic Potential:
The following adverse effects were reported in > 5% of patients with MDS treated with luspatercept in a Phase III trial. Severe or life-threatening adverse effects from other sources are also included.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Atrioventricular block (2%) | E | |||
| Heart failure (1%) | E | ||||
| Hypertension (9%) | E | ||||
| Thromboembolism (3%) (observed in thalassemia) | E | ||||
| Gastrointestinal | Anorexia (6%) | E | |||
| Constipation (11%) | E | ||||
| Diarrhea (22%) | E | ||||
| Nausea (20%) | E | ||||
| General | Fatigue (46%) | E | |||
| Hematological | Other (3%) - Extramedullary hematopoietic masses (reported in thalassemia) | E | |||
| Infection | Infection (11%) (including 1% sepsis; may be severe) | E | |||
| Injection site | Injection site reaction (5%) | E | |||
| Metabolic / Endocrine | Hyperglycemia (5%) | E | |||
| Musculoskeletal | Musculoskeletal pain (19%) | E | |||
| Neoplastic | Secondary malignancy (1%) (basal cell carcinoma) | D L | |||
| Nervous System | Dizziness (20%) | E | |||
| Headache (16%) | E | ||||
| Syncope (7%) (5% severe) | E | ||||
| Vertigo (6%) | E | ||||
| Renal | Nephrotoxicity (7%) (3% severe) | E | |||
| Respiratory | Cough, dyspnea (18%) | E | |||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
The most common side effects for luspatercept include fatigue, diarrhea, dizziness, nausea, musculoskeletal pain, cough, dyspnea, headache, constipation, and infection.
Grade 1-2 hypersensitivity reactions were reported in < 5% of patients and were non-serious.
Grade 1 injection site reactions were reported in < 5% of patients and were non-serious.
Hypertension has been reported in patients treated with luspatercept, with an average increase of 5 mmHg in systolic and diastolic pressure from baseline. Manage new-onset hypertension or exacerbations of pre-existing hypertension as clinically indicated.
Refer to protocol by which the patient is being treated.
Assess hemoglobin (Hgb) prior to each administration. If RBC transfusion occurred prior to dosing, pre-transfusion Hgb must be considered for dosing purposes.
Starting Dose:
Subcutaneous: 1 mg/kg every 3 weeks
Dose Titration Based on Response:
| Parameter | Action |
| Insufficient Response | |
|
After ≥ 2 consecutive doses (6 weeks) at 1 mg/kg:
|
Increase* dose to 1.33 mg/kg |
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After ≥ 2 consecutive doses (6 weeks) at 1.33 mg/kg:
|
Increase* dose to 1.75 mg/kg |
|
No reduction in RBC transfusion burden or no increase from baseline Hgb after ≥ 3 consecutive doses (9 weeks) at 1.75 mg/kg |
Discontinue. |
| Pre-dose Hgb ≥ 115 g/L or Rapid Hgb Rise | |
|
Pre-dose Hgb ≥ 115 g/L in the absence of transfusions |
Hold until Hgb is ≤ 110 g/L |
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Increase in Hgb > 20 g/L within 3 weeks in the absence of transfusion and: |
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*Do not increase dose more frequently than q6 weeks (2 doses) or exceed the maximum dose of 1.75 mg/kg or 168 mg.
| Toxicity | Action |
| Any Grade 2 adverse reaction | Hold until < Grade 1. |
| Grade 3 or 4 hypersensitivity reactions | Discontinue. |
| Grade 3 or 4 leukocytosis (>100,000 WBC/μL) | Hold until ≤ Grade 1. |
| Suspected hematologic malignancy | Hold and investigate; discontinue if confirmed. |
| Other Grade 3 or 4 adverse reactions | Hold until ≤ Grade 1. |
No dosage adjustments are required for patients with mild to severe hepatic impairment. Pharmacokinetic data are not available for patients with AST or ALT ≥ 3 x ULN.
| Approximate Creatinine Clearance* (mL/min) | Luspatercept Dose |
| ≥ 30 | No dosage adjustment required. |
| < 30 | No data; no dosage recommendations. |
*Reported as eGFR in mL/min/1.73 m2.
No dosage adjustments are required for patients ≥ 65 years of age.
Gender had no clinically significant effect on exposure.
Ethnicity (Asian versus Caucasian) had no clinically significant effect on exposure.
Luspatercept has not been evaluated in patients < 18 years of age.
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Reconstitute with SWFI and swirl gently to mix. Avoid aggressive shaking.
-
Administer by subcutaneous injection into the upper arm, thigh, and/or abdomen.
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Divide doses requiring larger volumes (i.e. > 1.2 mL) into separate injections and administer into separate sites.
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If a dose is missed, administer missed dose as soon as possible and continue dosing with at least 3 weeks between doses.
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Store vials refrigerated at 2-8˚C in original carton to protect from light. Do not freeze.
- Patients who are hypersensitive to this drug or any of its components
- Luspatercept is not a substitute for RBC transfusions in patients who require immediate correction of anemia.
Other Drug Properties:
-
Carcinogenicity:
Unknown
-
Mutagenicity:
Unknown
-
Embryotoxicity:
Yes
-
Fetotoxicity:
Yes
-
Pregnancy:
Luspatercept is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners during treatment, and for at least 3 months after the last dose.
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Breastfeeding:
Breastfeeding is not recommended during treatment, and for at least 3 months after the last dose.
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Excretion into breast milk:
Documented in animals
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Fertility effects:
Probable
Documented in studies with female animals, but effects were reversible.
No formal drug interaction studies have been conducted.
No clinically significant differences in luspatercept pharmacokinetics were observed when given concomitantly with iron-chelating agents.
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
| Monitor Type | Monitor Frequency |
|---|---|
CBC |
Baseline, prior to each dose, and as clinically indicated |
Blood pressure |
Baseline, prior to each dose, and as clinically indicated |
Liver function tests |
Baseline and as clinically indicated |
Renal function tests |
Baseline and as clinically indicated |
Clinical toxicity assessment for hypersensitivity, injection site reactions, infections, and cardiovascular effects |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Exceptional Access Program (EAP Website )
- luspatercept - For the treatment of red-blood cell (RBC) transfusion-dependent anemia associated with Myelodysplastic Syndromes (MDS), according to clinical criteria
CADTH Reimbursement Recommendation: Luspatercept (Reblozyl). Canadian Journal of Health Technologies. Dec 2021.
Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes.N Engl J Med 2020;382:140-51.
Kubasch AS, Fenaux P, Platzbecker U. Development of luspatercept to treat ineffective erythropoiesis. Blood Adv. 2021 Mar 9;5(5):1565-1575.
NCCN Guidelines. Antiemesis. May 24, 2023.
Prescribing information: REBLOZYL® (luspatercept-aamt). Celgene Corporation, a Bristol-Myers Squibb Company. /2023
Product monograph: REBLOZYL® (luspatercept). Bristol-Myers Squibb Canada. September 13, 2024.
July 2025 New drug monograph
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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