Luspatercept vs Epoetin in Treating Poor Erythroid Engraftment for Hematological Malignancies

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.

• Luspatercept (Drug): 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.
• Epoetin (Drug): Epoetin is administered 15000 IU subcutaneously every 3 weeks for 24 weeks

Primary outcomes

• Erythroid response [24 weeks]: Erythroid response is defined as a reduction in transfusion of ≥ 4 red blood cell units/8 weeks or a mean hemoglobin increase of ≥ 1.5 g/dL/8 weeks in the absence of transfusion

Secondary outcomes

• Overall survival [1 year]: Will calculate time from random assignment until death from any cause.
• Disease-free survival [1 year]: Will calculate time from random assignment until relapse or death from any cause
• Relapse [1 year]: Will calculate time from random assignment until relapse
• Non-relapse mortality [1 year]: Defined as death from any cause not subsequent to relapse

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

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• Qifa Liu, Principal investigator, Nanfang Hospital, Southern Medical University