Eltrombopag plus G-CSF for peripheral blood stem cell mobilization: Final analysis of a single arm, Phase 2 trial

Abstract Introduction Autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard treatment for relapsed/refractory lymphoma. However, 9% of patients in the plerixafor era still could not harvest adequate peripheral blood stem cells (PBSC) for auto-HSCT1. Thrombopoietin (TPO) receptor agonists have been shown to stimulate stem cell proliferation. This study aimed to determine whether the addition of eltrombopag improves the success rate of autologous PBSC harvest. Methods & Materials In this Phase 2, single-arm investigator-initiated trial, East-Asian patients with lymphomas scheduled to receive ESHAP chemo-mobilization for PBSC harvest were enrolled. Subjects receive eltrombopag at a dose of 75 mg daily from Day 6 of ESHAP until the end of PBSC harvest. The primary endpoint is the proportion of patients obtaining more than 2.0 × 106/kg CD34+ cells on the first apheresis day. Based on Simon's two-stage design, a total of 40 evaluable patients will be enrolled. If 29 or more patients meet the primary endpoint, we consider this intervention promising. A historical control with 50 patients who underwent PBSC harvest with ESHAP chemotherapy mobilization at the same institute in 2018 will be applied for comparison. Results As of August 2025, 39 patients had been enrolled. Their median age was 52 (range, 22-72); DLBCL was the most common diagnosis (53.85%, n=21). Despite one patient slot remaining to be filled, this trial has met its primary endpoint, with 29 of 39 patients enrolled obtaining more than 2.0 × 106/kg CD34+ cells on the first apheresis day. Compared to the historical control, the mean CD34+ cell quantity harvested on the first apheresis day was higher with the addition of eltrombopag administration (5.71 vs 13.30 × 106/kg, p = 0.02786). The major adverse events are ESHAP-related cytopenia with the severity comparable to that in the historical control. Eltrombopag-related adverse events were generally similar to those already known. No venous thromboembolism or severe hepatotoxicity was observed. After a median follow-up of 7.3 months, 37 out of 39 patients successfully proceeded with auto-HSCT, with no case of graft failure. The 12-month progression-free survival after auto-HSCT was 58.23%. The peak eltrombopag serum concentrations were available in 25 patients. The mean eltrombopag concentration across ESHAP D8 and D16 was 8.36 µg/mL. Compared to the pharmacokinetic data derived from a Caucasian cohort2, this concentration is 56.1% of that from healthy volunteers taking eltrombopag 100 mg/day. Interestingly, a higher peak eltrombopag serum concentration on ESHAP D8 correlated with a higher quantity of harvested CD34+ cells (Spearman's rank correlation, rho = 0.41, p = 0.04119), which is compatible with the proposed mechanism of action of this intervention. Conclusions Adding eltrombopag to stem cell mobilization for autologous PBSC harvest is safe and promising in improving PBSC harvest efficiency. The efficacy and long-term safety warrant further exploration with confirmatory studies. Reference Bone Marrow Transplant. 2018 Mar;53(3):246-254 J Clin Pharmacol. 2011 Mar;51(3):301-8