Luspatercept vs Epoetin in Treating Poor Erythroid Engraftment for Hematological Malignancies

Официальное название

Luspatercept Versus Epoetin in Treating Poor Erythroid Engraftment for Hematological Malignancies

Обзор

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for hematological malignancies. Nonetheless, poor graft function remains a life-threatening complication after allo-HSCT. Poor erythroid engraftment is associated with increased bleeding events and shorter survival. Current treatment methods such as epoetin or repeated red-cell transfusions are not effective for poor erythroid engraftment, with limited and transient responses. Retrospective studies suggested that luspatercept showed efficacy in patients with anemia post-transplantation or poor erythroid engraftment. However, there are no studies comparing luspatercept versus epoetin for the treatment of poor erythroid engraftment. Therefore, we conducted a randomized controlled study to compared the effect of luspatercept versus epoetin in treating poor erythroid engraftment for hematological malignancies.

Подробное описание

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for hematological malignancies. Nonetheless, poor graft function remains a life-threatening complication after allo-HSCT, characterized by persistent cytopenias despite evidence of complete donor chimerism. Poor erythroid engraftment refers to hemoglobin \<70g/L and inability to detach from red blood cell transfusion after 28 days of transplantation, which is associated with increased bleeding events and shorter survival. Current treatment methods such as epoetin or repeated red-cell transfusions are not effective for poor erythroid engraftment, with limited and transient responses. New treatment strategies are needed to enhance the response rate in patients with poor erythroid engraftment.

Luspatercept is a specific activin receptor fusion protein that reduces SMAD2 and SMAD3 signaling by binding specific transforming growth factor β (TGF-β) superfamily ligands, thereby allowing erythrocyte maturation through late-stage erythroblast differentiation. Retrospective studies suggested that luspatercept showed efficacy in patients with anemia post-transplantation or poor erythroid engraftment. To date, there have been no studies comparing luspatercept versus epoetin for the treatment of poor erythroid engraftment. Therefore, we conducted a randomized controlled study to compared the effect of luspatercept versus epoetin in treating poor erythroid engraftment for hematological malignancies.

Вмешательства

• Препарат Luspatercept
  Luspatercept is administered 1.0mg/kg subcutaneously every 3 weeks; If the hemoglobin level does not increase after two consecutive administrations, the dose will be adjusted to 1.3mg/kg. If the hemoglobin level returns to the normal range, Luspatercept will be given once before discontinuing the medication.
• Препарат Epoetin
  Epoetin is administered 15000 IU subcutaneously every 3 weeks for 24 weeks

Первичные конечные точки

• Erythroid response [Срок оценки: 24 weeks]

Вторичные конечные точки (4)

• Overall survival [Срок оценки: 1 year]
• Disease-free survival [Срок оценки: 1 year]
• Relapse [Срок оценки: 1 year]
• Non-relapse mortality [Срок оценки: 1 year]

Критерии участия

Критерии включения

• 18-65 years
• Hematologic malignancies
• Poor erythroid engraftment after the first allo-HSCT
• Complete remission post-transplantation
• Eastern Cooperative Oncology Group performance status of 0-2
• Epoetin-naive
• Endogenous serum erythropoietin concentration <500 U/L

Критерии исключения

• Life expectancy shorter than 30 days post-transplantation
• Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
• Patients with any conditions not suitable for the trial (investigators' decision)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Department of Hematology, Nanfang Hospital, Southern Medical University — Гуанчжоу

Публикации

• Della Porta MG, Garcia-Manero G, Santini V, Zeidan AM, Komrokji RS, Shortt J, Valcarcel D, Jonasova A, Dimicoli-Salazar S, Tiong IS, Lin CC, Li J, Zhang J, Pilot R, Kreitz S, Pozharskaya V, Keeperman KL, Rose S, Prebet T, Lai Y, Degulys A, Paolini S, Cluzeau T, Fenaux P, Platzbecker U. Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk mye PMID 39038479
• Tang C, Chen F, Kong D, Ma Q, Dai H, Yin J, Li Z, Chen J, Zhu X, Mao X, Wu D, Tang X. Successful treatment of secondary poor graft function post allogeneic hematopoietic stem cell transplantation with eltrombopag. J Hematol Oncol. 2018 Aug 16;11(1):103. doi: 10.1186/s13045-018-0649-6. PMID 30115080
• Markham A. Luspatercept: First Approval. Drugs. 2020 Jan;80(1):85-90. doi: 10.1007/s40265-019-01251-5. PMID 31939073
• Zhu L, Liu J, Liu H, et al. Clinical Study on the Treatment of Poor Erythroid Engraftment after Allogeneic Hematopoietic Stem Cell Transplantation with Luspatercept. Blood 2024; 144: 2159.
• Xin X, Zhang W, Li Z, Gui R, Wang J, Ji L, Zhang Y, Fang B, Song Y, Zu Y, Zhou J. Luspatercept for the treatment of anemia in allo-HSCT for patients with hematological diseases. Blood Cancer J. 2025 Feb 5;15(1):12. doi: 10.1038/s41408-025-01218-8. No abstract available. PMID 39910033

Идентификаторы

NCT: NCT07636486 · NFEC-2026-015

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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