Scholarlink

<p>Background: A proportion of transfusion-dependent β-thalassemia (TDT) patients show suboptimal or heterogeneous response to luspatercept. We explored a structured rescue approach by adding low- to moderate-dose thalidomide after predefined luspatercept failure in real-world practice. Methods: This study was a single-center retrospective cohort study. Adults with TDT on luspatercept who met predefined criteria for suboptimal response (failure to achieve ≥ 33% reduction in RBC units over a 12-week window versus each patient’s baseline 12-week window, or failure to increase Hb by ≥ 1.0 g/dL under an unchanged transfusion trigger) received thalidomide 25–50 mg once daily while continuing luspatercept. Primary endpoint was 12-week transfusion independence (TI), defined as no transfusion for 12 consecutive weeks and Hb ≥ 9.0 g/dL. Secondary endpoints included ≥ 33%/≥50% reductions in RBC units over matched 12-week windows, longitudinal Hb change, and safety graded by CTCAE v5.0 and reported as exposure-adjusted incidence rates. Results: Eleven patients were included (median age 23 years; female 45.5%; β⁰/β⁰ 18.2%; prior splenectomy 63.6%). Twelve-week transfusion independence (TI) was achieved in 4/11 patients (36.4%; 95% CI 15.2–64.6). Proportions with ≥ 33% and ≥ 50% reductions in RBC units over matched 12-week windows were 45.5% (95% CI 21.3–72.0) and 45.5% (95% CI 21.3–72.0), respectively. Hemoglobin increased by 4.0 g/dL (Hodges–Lehmann, 95% CI 2.9–5.0; LMM p &lt; 0.001). Total exposure was 112 patient-months; EAIR for any-grade treatment-emergent adverse events was 8.0 per 100 patient-months. No ≥Grade 2 neurotoxicity or thrombosis occurred. Conclusions: In TDT patients with predefined luspatercept failure, adding low- to moderate-dose thalidomide was associated with improvements in hemoglobin levels and reductions in transfusion burden with favorable tolerability. These findings warrant prospective validation of this structured rescue approach.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Low- to moderate-dose thalidomide combination rescue after luspatercept failure in transfusion-dependent β-thalassemia: a real-world cohort study

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月3日

查看全文
  • Soulivanh Nanthachak,
  • Cailan Wen,
  • Zhaoping Gan,
  • Lingyuan Pan,
  • Rongrong Liu,
  • Yumei Huang

摘要

Background: A proportion of transfusion-dependent β-thalassemia (TDT) patients show suboptimal or heterogeneous response to luspatercept. We explored a structured rescue approach by adding low- to moderate-dose thalidomide after predefined luspatercept failure in real-world practice. Methods: This study was a single-center retrospective cohort study. Adults with TDT on luspatercept who met predefined criteria for suboptimal response (failure to achieve ≥ 33% reduction in RBC units over a 12-week window versus each patient’s baseline 12-week window, or failure to increase Hb by ≥ 1.0 g/dL under an unchanged transfusion trigger) received thalidomide 25–50 mg once daily while continuing luspatercept. Primary endpoint was 12-week transfusion independence (TI), defined as no transfusion for 12 consecutive weeks and Hb ≥ 9.0 g/dL. Secondary endpoints included ≥ 33%/≥50% reductions in RBC units over matched 12-week windows, longitudinal Hb change, and safety graded by CTCAE v5.0 and reported as exposure-adjusted incidence rates. Results: Eleven patients were included (median age 23 years; female 45.5%; β⁰/β⁰ 18.2%; prior splenectomy 63.6%). Twelve-week transfusion independence (TI) was achieved in 4/11 patients (36.4%; 95% CI 15.2–64.6). Proportions with ≥ 33% and ≥ 50% reductions in RBC units over matched 12-week windows were 45.5% (95% CI 21.3–72.0) and 45.5% (95% CI 21.3–72.0), respectively. Hemoglobin increased by 4.0 g/dL (Hodges–Lehmann, 95% CI 2.9–5.0; LMM p < 0.001). Total exposure was 112 patient-months; EAIR for any-grade treatment-emergent adverse events was 8.0 per 100 patient-months. No ≥Grade 2 neurotoxicity or thrombosis occurred. Conclusions: In TDT patients with predefined luspatercept failure, adding low- to moderate-dose thalidomide was associated with improvements in hemoglobin levels and reductions in transfusion burden with favorable tolerability. These findings warrant prospective validation of this structured rescue approach.