Efficacy and Safety of Single-Dose Versus Split-Dose Mecapegfilgrastim with Etoposide for Autologous Peripheral Blood Stem Cell Mobilization: A Prospective, Randomized Clinical Trial

High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (auto-HSCT) is a well-established consolidation treatment for lymphoma and multiple myeloma, reducing relapse risk and improving survival. Effective mobilization of peripheral blood stem cells (PBSC), measured by the collection of an adequate number of CD34+ cells, is critical for successful auto-HSCT. Mecapegfilgrastim, a novel pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF), offers a stable structure, low immunogenicity and extended half-life. Despite its growing use in PBSC mobilization for hematological malignancies, data on its efficacy in different dosing regimens remain scarce. This study evaluates the efficacy and safety of single-dose versus split-dose mecapegfilgrastim combined with high-dose etoposide for PBSC mobilization in patients with lymphoma and multiple myeloma.

In this prospective, randomized, controlled, single-center clinical trial, 57 patients (25 with lymphoma, 32 with multiple myeloma) undergoing autologous PBSC mobilization were recruited between July 2021 and March 2024. Participants were randomized into two groups based on the mecapegfilgrastim administration pattern: a split-dose group (n=30) receiving 6 mg on days 3 and 7, and a single-dose group (n=27) receiving 12 mg on day 3. All the patients received etoposide (1.6 g/m² over 10 hours) on day 1. Apheresis was performed based on the peripheral blood CD34+ cell count (≥10 cells/μL) or a risk-benefit assessment. Primary endpoint was the rate of successful mobilization (≥2×10⁶ CD34+ cells/kg).

Baseline characteristics, including age, sex, Eastern Cooperative Oncology Group (ECOG) status, underlying disease, previous chemotherapy cycles, and prior exposure to lenalidomide, bendamustine, and radiotherapy, were comparable between the two groups. The median day for the first collection was day 8 (range 8-10) in both groups. The split-dose group achieved a significantly higher optimal mobilization rate (≥5×10⁶ CD34+ cells/kg) of the first collection compared with the single-dose group (56.7% vs. 25.9%, P=0.019), though there was no significant difference in the success mobilization rate (70.0% vs. 66.7%, P=0.787). After two collections, the differences in mobilization rates were not statistically significant: optimal mobilization (70.0% vs. 59.3%, P=0.396) and successful mobilization (76.7% vs. 77.8%, P=0.920). Overall, the split-dose regimen showed a trend towards greater efficiency, but the differences were not statistically significant (successful mobilization: 90.0% vs. 81.5%, P=0.355; optimal mobilization: 76.7% vs. 70.4%, P=0.590). The number of apheresis procedures required for successful mobilization was 1 (range 1-4) in the split-dose group and 1 (range 1-3) in the single-dose group, while for optimal mobilization, the split-dose group required 1 (range 1-3) and the single-dose group required 2 (range 1-3). Median days to hematopoietic reconstitution post-transplantation did not differ significantly (neutrophil: 10 vs. 9.5 days, P=0.689; platelet: 11 vs. 12 days, P=0.632).

The incidence of treatment-emergent adverse events (TEAEs) was comparable between groups. Common grade 3 or higher TEAEs included thrombocytopenia (86.7% in the split-dose group vs. 100% in the single-dose group), neutropenia (96.7% vs. 96.3%), anemia (36.7% vs. 22.2%), and febrile neutropenia (20.0% vs. 14.8%). No treatment-related serious adverse events were reported in either group.

In conclusion, both single-dose and split-dose regimens of mecapegfilgrastim combined with etoposide are effective and safe for PBSC mobilization in lymphoma and multiple myeloma patients. The split-dose regimen demonstrated a superior optimal mobilization rate at the first collection, suggesting that it may offer a more efficient mobilization approach. The combination of mecapegfilgrastim and high-dose etoposide represents a promising strategy for PBSC mobilization, which merits further investigation.