Luspatercept

Summary

Luspatercept (Reblozyl) is an erythroid maturation agent approved for the treatment of anemia in adults with beta-thalassemia requiring regular red blood cell transfusions and for anemia in adults with myelodysplastic syndromes (MDS) with ring sideroblasts or MDS/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis. It acts as a ligand trap for TGF-β superfamily members to enhance late-stage erythropoiesis.

Mechanism of Action

Binds and inhibits TGF-β superfamily ligands (including GDF11, activin B, GDF8) that negatively regulate late-stage erythropoiesis, thereby promoting red blood cell maturation and reducing ineffective erythropoiesis

Routes of Administration

Goals & Uses

• Treatment of anemia in lower-risk MDS (non-RS)Hematologic / InvestigationalModerate
• Reduction of transfusion burden in beta-thalassemiaHematologic / Anemia ManagementHigh
• Treatment of anemia in MDS with ring sideroblastsHematologic / Anemia ManagementHigh
• Improvement of erythropoiesis in myelofibrosis-associated anemiaHematologic / InvestigationalModerate

Contraindications

• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Known hypersensitivity to luspatercept or excipientsAllergyHigh

Adverse Effects

• HypertensionCardiovascularCommonHigh blood pressure
• HeadacheNeurologicCommonPain in the head or upper neck
• Thromboembolic eventsCardiovascularUncommon
• Musculoskeletal pain (bone pain, arthralgia, myalgia)MusculoskeletalCommon
• FatigueGeneralCommonLow energy or tiredness
• DizzinessNeurologicCommonFeeling faint, lightheaded, or unsteady

Drug Interactions

• Erythropoiesis-stimulating agents (ESAs)Moderate

Population Constraints

• Pediatric patients (<18 years)AgeRelative
• Patients with severe hepatic impairmentHepaticRelative
• Patients with severe renal impairmentOrgan ImpairmentRelative
• Splenectomized patientsSurgical HistoryRelative

Regulatory Status

• European UnionApprovedApproved: Anemia in adults with transfusion-dependent beta-thalassemia, Anemia in adults with MDS with ring sideroblasts or MDS/MPN with ring sideroblasts and thrombocytosisEMA approved June 25, 2020; marketed as Reblozyl by Bristol Myers Squibb
• United StatesApprovedApproved: Anemia failing an ESA and requiring ≥2 RBC units/8 weeks in adults with very low- to intermediate-risk MDS, Anemia in adults with beta-thalassemia who require regular RBC transfusions, Anemia in adults with MDS-associated ring sideroblasts or MDS/MPN-RS-TFDA approved November 8, 2019 (beta-thalassemia); June 2020 (MDS-RS); April 2023 (lower-risk MDS broader label expansion)
• United KingdomApprovedApproved: Anemia in adults with transfusion-dependent beta-thalassemia, Anemia in adults with MDS with ring sideroblastsMHRA approved; NICE technology appraisals have evaluated use in MDS and beta-thalassemia with conditional recommendations

FDA approved November 2019 for beta-thalassemia; expanded approval June 2020 for MDS-RS; EMA approved June 2020. Developed by Acceleron Pharma and Bristol-Myers Squibb (now Bristol Myers Squibb/Merck). Black box warning: Thromboembolic events. REMS not required.

Evidence & Sources

No sources recorded yet.