Romiplostim N01 enhances platelet engraftment in ASCT using non-cryopreserved pbscs for plasma cell neoplasms: A single-center phase II study in China

Abstract

Abstract Autologous hematopoietic stem cell transplantation (ASCT) remains a standard of care for plasma cell neoplasms, including multiple myeloma (MM) and AL amyloidosis. However, delayed platelet engraftment (DPE) following high-dose conditioning remains a clinical challenge. Use of non-cryopreserved peripheral blood stem cells (PBSCs) and thrombopoietin receptor agonists has been explored to overcome this limitation. This study evaluated the efficacy and safety of Romiplostim N01 in facilitating platelet engraftment in patients undergoing ASCT with non-cryopreserved PBSCs. This was a investigator-initiated, single-center, open-label study conducted from May 2024 to June 2025. Patients received Melphalan conditioning followed by infusion of non-cryopreserved PBSCs stored for ≤48 hours at 4℃. Romiplostim N01 was administered weekly from day +1 post-ASCT until platelet count ≥75×10⁹/L. Historical controls underwent ASCT with cryopreserved PBSCs between January 2022 and December 2024 and received recombinant human thrombopoietin (rhTPO; 300 U/kg/day) upon platelet count <75×10⁹/L. The primary endpoint was time to platelet engraftment. Secondary endpoints included time to neutrophil engraftment, transfusion requirements, hospitalization metrics, safety, and survival. A total of fifteen patients were undergoing non-cryopreserved PBSCs ASCT with Romiplostim N01 support (Romiplostim group, n=15), while the historical control group (Control group, n=21) included twenty-one patients who received cryopreserved PBSCs ASCT combined with rhTPO to promote engraftment. The Romiplostim group included 12 MM patients and 3 AL amyloidosis patients, while the control group included 20 MM patients and 1 AL amyloidosis patient. The Romiplostim group comprised 11 males and 4 females, compared with 13 males and 8 females in the control group. The median age was 59.8 years [range 50-79 years] in the Romiplostim group and 61 years [range 45-78 years] in the control group, with no significant differences observed in any of these parameters (P<0.05). The median infused CD34+ stem cell dose was 4.53 ×106/Kg (range 1.26 to 10.05×106/Kg) in the Romiplostim group and 5.60 ×106/Kg (range 1.24 to 22.04×106/Kg) in the control group, which was not statistically different (P= 0.499). Median time from diagnosis to transplant was significantly shorter in the Romiplostim group (5.5 months; range 3-9) vs controls (7 months; range 5-32; P=0.002), as was the median number of induction cycles (4 [2-6] vs 5 [4-16]; P=0.024). Other baseline characteristics were also comparable, such as Durie-Salmon stage, R-ISS stage, HCT-CI scpre, disease response prior to HSCT, Plerixafor use, single day apheresis and Melphalan dose. All patients achieved hematologic engraftment. Median time to platelet engraftment was significantly shorter with Romiplostim (11 days [range 8–16]) vs controls (13 days [range 9–20], P=0.008). Time to neutrophil recovery and platelet transfusion requirements were similar between groups. No significant differences were observed in incidence of mucositis, diarrhea, febrile neutropenia, documented infections, or organ toxicities. While length of hospitalization was comparable, total costs were significantly lower in the Romiplostim group, attributed to the omission of cryopreservation and lower drug cost compared to rhTPO. At a median follow-up of 10.8 months, 2-year overall survival did not differ significantly (85.7% ± 13.2% vs 84.4% ± 8.3%, P=0.717). In patients with plasma cell neoplasms undergoing ASCT with non-cryopreserved PBSCs, Romiplostim N01 significantly accelerated platelet engraftment and reduced hospitalization costs without compromising safety. These findings support its use as an effective alternative to traditional cryopreserved PBSCs with rhTPO support.