P141 | Luspatercept Treatment in Patients With Transfusion-dependent Beta-thalassemia: a Single-center Experience
Year: 2025
Type: article
Abstract: Background: Luspatercept is a drug that promotes erythroblast maturation and increases the production of mature endogenous red blood cells by blocking specific TGF-β ligands and inhibiting aberrant Smad2/3 signaling. In the BELIEVE study, Luspatercept reduced transfusion burden by at least 33% in 21.4% of patients with transfusion-dependent beta-thalassemia (TDT), between weeks 13-24. Aims: The aim of our retrospective study is to analyze the reduction in transfusion burden of at least 33% over 24 weeks and toxicity of Luspatercept in a single-center cohort of patients with TDT. Methods: Data from 20 patients over 18 years of age, affected by TDT and treated with Luspatercept from 2016 to 2024 at our center were analyzed. All had ECOG 0; the average age at drug initiation was 41 years. Eleven patients were splenectomized, 4 patients had splenomegaly; B0/B0 genotype was present in 4 patients. The average number of administrations was 20 doses. Results: Treatment with Luspatercept was administered to a total of 20 patients. Of these, 15 were treated for 24 weeks, and only 8 are currently continuing treatment due t adverse eents. Bone pain was reported in 8 patients, hypertension in 4, neurological symptoms in 2, venous thrombosis in 2, weight loss in 1, and expansion of extramedullary hematopoietic foci in 1. Only two adverse events were grade ≥2, and none were grade ≥3. Only 3 out of 15 patients achieved the reduction >33% in transfusion needs; in 7 there was a reduction> 20% (Tab. 1); an additional patient showed an improvement in pretransfusion hemoglobin levels, which increased by 0.7 g/dL. No patient experienced a delayed reduction between weeks 48 and 72. Conclusions: At our center, reductions in transfusion burden of >33% were lower than expected and occurred exclusively in patients with a non-B0/B0 genotype. Nevertheless, 7 patients showed a reduction in transfusion requirements, though lower (>20%). Adverse events occurred in a higher number of cases compared to BELIEVE study, and while some were manageable with pharmacological treatment, many patients opted to stop therapy. In the future we hope that the routine use of luspatercept in the clinical practice of thalassemia centers, combined with better patients stratification for its prioritized use, will change patients' appoach to the drug, leading to a lower number of discontinuation.
Authors: M. Schirru, P. Carrara, M. Lamagna, V.M. Pinto, S. Quintino, M. Balocco
Institutions: University of Genoa, Ente Ospedaliero Ospedali Galliera
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093121554
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