Efficacy and safety observation of luspatercept for refractory anemia associated with hematologic malignanciesluspatercept治疗血液系统恶性肿瘤相关难治性贫血的疗效和安全性观察luspatercept 改善与血液系统恶性肿瘤相关的难治性贫血的疗效和安全性：一项观察

Abstract

Abstract Background: Patients with hematologic malignancies often experience anemia of varying severity. This anemia impedes blood count recovery post-chemotherapy and compromises cardiopulmonary function and immunity. Currently, transfusion is the primary symptomatic treatment for anemia in this population. However, due to blood product shortages, transfusion criteria are stringent, typically reserved for chronic anemia with hemoglobin (Hb) levels below 60 g/L. Luspatercept, recently approved for transfusion-dependent low-risk myelodysplastic syndromes (MDS) or β-thalassemia, promotes erythroid maturation. Its potential efficacy in reducing anemia and its safety profile regarding malignant transformation risk in non-indicated patients remain unexplored in clinical studies. Methods: We conducted a retrospective clinical study involving 22 patients with hematologic malignancies treated at Ningbo University Affiliated First Hospital between March 1, 2024, and February 28, 2025, all outside the approved indications for Luspatercept. As this constituted off-label use, all patients provided informed consent. Based on the Luspatercept prescribing information and guidelines, treatment was initiated at 1 mg/kg subcutaneously every 3 weeks. After two doses, if the transfusion burden reduction was <33% or Hb increase was <1 g/dL in non-transfused patients, the dose was escalated stepwise (1.25 mg/kg → 1.5 mg/kg → maximum 1.75 mg/kg). Results: Among 20 patients, Hb levels increased within 1-14 days post-treatment. Mean Hb rose significantly from 60.61 g/L pre-treatment to 96.21 g/L post-treatment (mean increase: 39.56 g/L). Hb levels exceeded 100 g/L in 9 patients. Transfusion Reduction: Pre-treatment, 16 patients required red blood cell (RBC) transfusions. Post-treatment, only 7 required transfusions, with 9 patients achieving transfusion independence.Treatment Response in Transfusion-Dependent (TD) Patients:Among the 7 patients still requiring transfusions, 6 showed transient Hb elevation within the first week followed by decline. Their RBC requirement decreased minimally (mean monthly units: 4.2U pre- vs. 4.1U post-treatment), suggesting treatment failure. Treatment Response in Non-Transfusion-Dependent (NTD) Patients:of 6 NTD patients pre-treatment, 5 showed an Hb increase of ≥10 g/L; 1 had only a 4 g/L increase (treatment failure). The overall response rate was 63.6% (14/22). Response rates were: 56.3% (9/16) in TD patients. 83.3% (5/6) in NTD patients. Conclusion: Luspatercept demonstrates safe and effective management of refractory anemia in patients with hematologic malignancies. Further clinical studies are warranted to precisely identify patient subgroups most likely to benefit from Luspatercept therapy.