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

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 × 10(9)/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).