Note: Assess Hb and transfusion history prior to each dose. If an RBC transfusion occurred prior to the dose, use pretransfusion Hb for dosing evaluation purposes.
Anemia due to beta thalassemia: SubQ: Initial: 1 mg/kg once every 3 weeks (Cappellini 2020).
Luspatercept Dosing Recommendationa | |
---|---|
aDo not increase the dose if patient is experiencing an adverse reaction. | |
Starting dose |
1 mg/kg once every 3 weeks |
Maximum dose |
1.25 mg/kg once every 3 weeks |
Dose increases for insufficient response at initiation of treatment | |
No reduction in RBC transfusion burden after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose |
Increase the dose to 1.25 mg/kg once every 3 weeks (maximum dose) |
No reduction in RBC transfusion burden after 3 consecutive doses (9 weeks) at 1.25 mg/kg |
Discontinue luspatercept |
Dose modifications for predose hemoglobin levels or rapid hemoglobin rise | |
Predose hemoglobin ≥11.5 g/dL (in the absence of transfusions): Interrupt luspatercept; resume when hemoglobin is ≤11 g/dL | |
Increase in hemoglobin >2 g/dL within 3 weeks (in the absence of transfusions) and Current dose is 1.25 mg/kg: Reduce dose to 1 mg/kg once every 3 weeks Current dose is 1 mg/kg: Reduce dose to 0.8 mg/kg once every 3 weeks Current dose is 0.8 mg/kg: Reduce dose to 0.6 mg/kg once every 3 weeks Current dose is 0.6 mg/kg: Discontinue luspatercept | |
Dose modification for adverse reactionsa | |
Hypersensitivity reaction, grade 3 or 4 |
Discontinue luspatercept |
Other grade 3 or 4 adverse reactions |
Interrupt luspatercept therapy; resume when the adverse reaction resolves to ≤ grade 1. |
Anemia due to myelodysplastic syndromes with ring sideroblasts or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis: SubQ: Initial: 1 mg/kg once every 3 weeks (Fenaux 2020).
Luspatercept Dosing Recommendationa | |
---|---|
aDo not increase the dose if patient is experiencing an adverse reaction. | |
Starting dose |
1 mg/kg once every 3 weeks |
Maximum dose |
1.75 mg/kg once every 3 weeks |
Dose increases for insufficient response at initiation of treatment | |
Not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose |
Increase the dose to 1.33 mg/kg once every 3 weeks |
Not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at 1.33 mg/kg dose |
Increase the dose to 1.75 mg/kg once every 3 weeks (maximum dose) |
No reduction in RBC transfusion burden after 3 consecutive doses (9 weeks) at 1.75 mg/kg |
Discontinue luspatercept |
Dose modifications for predose hemoglobin levels or rapid hemoglobin rise | |
Predose hemoglobin ≥11.5 g/dL (in the absence of transfusions): Interrupt luspatercept; resume when hemoglobin is ≤11 g/dL. | |
Increase in hemoglobin >2 g/dL within 3 weeks (in the absence of transfusions) and Current dose is 1.75 mg/kg: Reduce dose to 1.33 mg/kg once every 3 weeks Current dose is 1.33 mg/kg: Reduce dose to 1 mg/kg once every 3 weeks Current dose is 1 mg/kg: Reduce dose to 0.8 mg/kg once every 3 weeks Current dose is 0.8 mg/kg: Reduce dose to 0.6 mg/kg once every 3 weeks Current dose is 0.6 mg/kg: Discontinue luspatercept | |
Dose modification for adverse reactionsa | |
Hypersensitivity reaction, grade 3 or 4 |
Discontinue luspatercept |
Other grade 3 or 4 adverse reactions |
Interrupt luspatercept therapy; resume at the next lower dose level when the adverse reaction resolves to ≤ grade 1. If the dose delay is >12 consecutive weeks, discontinue luspatercept. |
Missed dose: If a dose is delayed or missed, administer as soon as possible and continue the regular dosing schedule (with at least 3 weeks between doses).
eGFR 30 to 89 mL/minute/1.73 m2: No clinically significant pharmacokinetic differences were observed in patients with mild to moderate renal impairment; dosage adjustment is likely not necessary.
eGFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Total bilirubin ≤ ULN and AST or ALT > ULN or total bilirubin > ULN and any AST or ALT: No clinically significant pharmacokinetic differences were observed in patients with hepatic impairment; dosage adjustment is likely not necessary.
AST or ALT >3 times ULN: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Subcutaneous [preservative free]:
Reblozyl: Luspatercept-aamt 25 mg (1 ea); Luspatercept-aamt 75 mg (1 ea) [contains polysorbate 80]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Subcutaneous:
Reblozyl: 25 mg (1 ea); 75 mg (1 ea) [contains polysorbate 80]
Luspatercept is available only through authorized distributors. For further information on patient assistance, product availability, and prescribing instructions, please refer to the following website: https://www.reblozylpro.com/.
SubQ: Inject into the upper arm, thigh, and/or abdomen. Doses requiring larger reconstituted volumes (>1.2 mL) should be divided into separate syringes with similar volumes; inject into separate sites. Use a new syringe and needle for each separate injection. If refrigerated, allow reconstituted solution to come to room temperature for 15 to 30 minutes prior to injection.
Anemia due to beta thalassemia: Treatment of anemia in adults with beta thalassemia who require regular RBC transfusions.
Anemia due to myelodysplastic syndromes with ring sideroblasts or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis: Treatment of anemia failing an erythropoiesis-stimulating agent and requiring 2 or more RBC units over 8 weeks in adults with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
Limitations of use: Luspatercept is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.
Luspatercept may be confused with etanercept, lusutrombopag, Lupron.
Reblozyl may be confused with Rebetol, Rebif, Rebinyn.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypertension (8% to 11%)
Gastrointestinal: Abdominal pain (14%), diarrhea (12% to 16%), nausea (9% to 16%)
Hepatic: Increased serum alanine aminotransferase (9% to 12%), increased serum aspartate aminotransferase (4% to 11%), increased serum bilirubin (12% to 64%)
Nervous system: Dizziness (≤18%), fatigue (14% to 41%), headache (14% to 26%), vertigo (≤18%)
Neuromuscular & skeletal: Arthralgia (19%), musculoskeletal pain (20%), ostealgia (20%)
Renal: Decreased creatinine clearance (27%)
Respiratory: Cough (14%), dyspnea (13%)
1% to 10%:
Cardiovascular: Cerebrovascular accident (1%), deep vein thrombosis (≤4%), ischemic stroke (≤4%), portal vein thrombosis (≤4%), presyncope (≤5%), pulmonary embolism (≤4%), syncope (≤5%), tachycardia (8%)
Endocrine & metabolic: Hyperuricemia (7%)
Genitourinary: Urinary tract infection (<5%)
Hepatic: Increased direct serum bilirubin (6%), increased serum alkaline phosphatase (8%)
Hypersensitivity: Hypersensitivity reaction (≤10%)
Immunologic: Antibody development (1% to 9%; neutralizing: ≤4%)
Infection: Influenza (≤9%; flu-like symptoms: ≤6%)
Local: Injection site reaction (≤7%)
Renal: Renal insufficiency (8%)
Respiratory: Bronchitis (<5%), upper respiratory tract infection (7%), viral upper respiratory tract infection (6%)
Frequency not defined: Neuromuscular & skeletal: Back pain
There are no contraindications listed in the US manufacturer's labeling.
Canadian labeling: Hypersensitivity to luspatercept or any component of the formulation.
Concerns related to adverse effects:
• Hypertension: Hypertension has been reported, including grade 3 and 4 events. Some patients with normal baseline BP developed elevated systolic BP (≥130 mm Hg) and/or elevated diastolic BP (≥80 mm Hg). Monitor BP prior to each luspatercept dose and as clinically necessary. Manage new-onset or worsened preexisting hypertension with appropriate antihypertensive therapy.
• Musculoskeletal adverse reactions: Bone pain and arthralgia have been reported in ~20% of patients receiving luspatercept in clinical trials, although the majority of events were mild (grade 1 or 2).
• Thromboembolic events: Thromboembolic events, including deep vein thrombosis, pulmonary embolus, portal vein thrombosis, and ischemic strokes, have been reported in a small number of patients with beta thalassemia receiving luspatercept in clinical trials. Patients with risk factors for thromboembolism such as splenectomy or concomitant use of hormone replacement therapy may be at increased risk of thromboembolic events. Monitor for signs/symptoms of thrombosis/thromboembolism. Thromboprophylaxis may be considered in patients with elevated risk for thromboembolic events.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
None known.
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use effective contraception during luspatercept therapy and for ≥3 months after the last luspatercept dose.
Based on data from animal reproduction studies, in utero exposure to luspatercept may cause fetal harm.
It is not known if luspatercept is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 3 months after the last luspatercept dose.
Assess Hb prior to each luspatercept dose; evaluate pregnancy status prior to initiation (in females of reproductive potential); monitor blood pressure prior to each dose and as clinically necessary. Monitor for signs/symptoms of thromboembolism.
Luspatercept is a recombinant fusion protein that contains a modified form of the extracellular domain of human activin receptor type IIb and links to the human IgG1 Fc domain. It binds several endogenous transforming growth factor-beta (TGF-β) superfamily ligands, which results in reduced Smad2/3 signaling. Inhibition of TGF-β superfamily results in increased differentiation and proliferation of erythroid precursors and improves hematology parameters associated with ineffective erythropoiesis.
Onset: Hb increased within 7 days of luspatercept initiation (in patients receiving <4 units of RBCs within 8 weeks prior to dose).
Duration: Hb levels returned to baseline ~6 to 8 weeks from the last dose.
Distribution: Vd: Beta thalassemia: 7.1 L; Myelodysplastic syndromes (MDS): 9.7 L.
Metabolism: Expected to be catabolized into amino acids via general protein degradation processes in multiple tissues.
Half-life elimination: Beta thalassemia: ~11 days; MDS: ~13 days.
Time to peak: Median: Beta thalassemia: ~7 days (range: 6 to 10 days); MDS: ~7 days (range: 5 to 21 days).
Excretion: Clearance: Beta thalassemia: 0.44 L/day; MDS: 0.52 L/day.
Weight: The apparent clearance and volume of distribution of luspatercept increased with increasing body weight (34 to 97 kg) in patients with beta thalassemia; 46 to 124 kg in patients with myelodysplastic syndromes.
Solution (reconstituted) (Reblozyl Subcutaneous)
25 mg (per each): $4,318.04
75 mg (per each): $12,954.11
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