Oral eltrombopag versus subcutaneous recombinant human thrombopoietin for promoting platelet engraftment after allogeneic stem cell transplantation: A prospective, non-inferiority, randomized controlled trial

Abstract

Delayed platelet engraftment (DPE) is associated with poor survival and increased transplantation-related mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, treatments are needed to improve platelet engraftment and prevent DPE. We performed a phase three, non-inferior, randomized controlled study of eltrombopag or recombinant human thrombopoietin (rhTPO) to promot platelet engraftment after allo-HSCT. Candidates for allo-HSCT were randomly assigned to receive oral eltrombopag (50 mg daily) or subcutaneous rhTPO (15000U daily) from the first-day post-transplantation. The primary endpoint was the cumulative numbers of platelet engraftment (platelet recovery ≥20 × 10⁹ /L, without transfusion, for seven consecutive days) on day 60 after transplantation. We performed intention-to-treat analyses with a non-inferior margin of -15%. A total of 92 participants underwent randomization. 44 and 48 patients were randomized to the eltrombopag and rhTPO groups, respectively. The median duration of follow-up was 360 days (range: 12-960 days). The cumulative incidence of platelet engraftment on day 60 after transplantation in eltrombopag group was 86.4% (38/44) compared with 85.4% (41/48) in the rhTPO group (absolute risk difference [ARD] 1%, one-sided lower limit of 95% confidence interval [CI] -13.28%, P_{non-inferirioty} = 0.014). The rate of DPE in the eltrombopag group was 6.8% (3/44) compared with 12.5% (6/48) in the rhTPO group (ARD -5.7%, one-sided higher limit of 95% CI 6.28%, P_{non-inferirioty} = 0.063). Approximately, three-fourths of non-hematologic adverse events were not observed in the eltrombopag group but three patients (3/48, 6%) experienecd them in the rhTPO group. In addition, platelet transfusions unite from day 0 to day 21, or from day 22 to day 60, progression-free survival, overall survival were not significantly different between both groups. Eltrombopag was non-inferior to rhTPO in promoting platelet engraftment post allo-HSCT for patients with hematological malignancy. Oral eltrombopag was more convenient for patients than subcutaneous rhTPO (NCT03515096).

Keywords: allogeneic stem cell transplantation; eltrombopag; platelet engraftment; recombinant human thrombopoietin; rhTPO.

FIGURE 1

Randomization and treatment

FIGURE 2

The cumulative incidence of platelet engraftment on day 60 post transplantation in eltrombopag and eltrombopag or recombinant human thrombopoietin (rhTPO) groups

FIGURE 3

The cumulative incidence of total platelet engraftment, platelet engraftment on day 60, and Delayed platelet engraftment (DPE) post transplantation in eltrombopag and eltrombopag or recombinant human thrombopoietin (rhTPO) groups

FIGURE 4

The mean units of platelets transfusion from day 0 to days 21, day 21 to days 60 post transplantation in eltrombopag and eltrombopag or recombinant human thrombopoietin (rhTPO) groups

FIGURE 5

Progression‐free survival (PFS) and overall survival (OS) in eltrombopag and eltrombopag or recombinant human thrombopoietin (rhTPO) groups

FIGURE 6

Immune recovery on day 30 post‐transplantation in eltrombopag and eltrombopag or recombinant human thrombopoietin (rhTPO) groups