Eltrombopag for Post-Transplantation Thrombocytopenia: Results of Phase II Randomized, Double-Blind, Placebo-Controlled Trial

Abstract Prolonged thrombocytopenia occurs in up to 37% of patients after hematopoietic stem cell transplantation (HSCT) and is associated with adverse prognosis and increased risk of bleeding. Eltrombopag, a thrombopoietin receptor agonist, can increase platelet counts in thrombocytopenic patients. We conducted a phase II study, adaptively randomizing patients ≥35 days post-HSCT to receive placebo or eltrombopag if platelet count ≤ 20,000/µL for seven days or platelet transfusion-dependent, and neutrophil count ≥ 1500/µL. Sixty patients were randomized to eltrombopag (n=42) or placebo (n=18) and received at least one dose. Fifteen (36%) patients in the eltrombopag arm achieved a platelet count of ≥ 30,000/µL compared to five (28%) patients in the placebo arm, the posterior probability 0.75 (the protocol required this probability to be > 0.975 to declare a winner; thus, the results are inconclusive). However, nine (21%) patients in the eltrombopag arm achieved a platelet count of ≥ 50,000/µL compared to no (0%) patient in the placebo arm, p=0.046. The overall survival, progression-free survival, relapse rate, and non-relapse mortality were similar in two arms. In conclusion, compared to placebo, treatment with eltrombopag led to a higher percentage of patients achieving a platelet count of ≥ 50,000/µL in patients with persistent thrombocytopenia after HSCT. (ClinicalTrials.gov identifier, NCT01000051)