Efficacy and safety of romiplostim N01 combined with cyclosporine in refractory aplastic anemia patients：a multicenter phase II study

Abstract Background: Patients with aplastic anemia (AA) who are refractory to immunosuppressive therapy (IST) combined with thrombopoietin receptor agonists (TPO-RAs) face poor clinical outcomes and limited evidence-based treatment options. Romiplostim N01 is a biosimilar of romiplostim (Nplate®), a TPO-RA approved in China for the treatment of primary immune thrombocytopenia (ITP). However, its optimal dosing, efficacy, and safety profile in refractory AA remain unclear. This prospective, open-label, multicenter phase II trial (ChiCTR2400085301) aims to evaluate the efficacy and safety of romiplostim N01 in combination with cyclosporine in patients with refractory AA. Methods Eligible patients had been previously treated with standard IST (cyclosporine and/or anti-thymocyte globulin) plus TPO-RA (eltrombopag or hetrombopag) for at least 3 months without response. All enrolled patients received romiplostim N01 in combination with cyclosporine (3–5 mg/kg/day). Romiplostim N01 was initiated at 10 µg/kg weekly, with dose escalation by 5 µg/kg every 2 weeks in patients without at least a single-line hematologic response, up to a maximum of 20 µg/kg. The total treatment duration was 26 weeks. The primary endpoint was hematologic response at week 26. Results As of July 31, 2025, 16 patients were enrolled (target: 40); 11 patients completed the 26-week follow-up. All patients had platelet counts <30×10⁹/L at baseline and were classified as non-responders to prior IST plus eltrombopag or hetrombopag. At enrollment, 6/11 (54.5%) met criteria for severe AA (SAA), 1/11 (9.1%) for transfusion-dependent non-severe AA (TD-NSAA), and 4/11 (36.4%) for non–transfusion-dependent NSAA (NTD-NSAA). At week 13, the overall response rate (ORR) was 81.8% (9/11), with a complete response (CR) in 9.1%(1/11). At week 26, the ORR remained 81.8% (9/11), and the CR rate increased to 18.2%(2/11). No treatment-related adverse events leading to discontinuation were observed.Conclusions: Romiplostim N01 in combination with cyclosporine demonstrated promising efficacy and a favorable safety profile in patients with AA refractory to multiple TPO-RAs plus IST. These preliminary results support further investigation of this combination as a therapeutic option for refractory AA.