Safety and efficacy of Efbemalenograstim alfa for patients at risk for chemotherapy-induced neutropenia: A Systematic review and Meta-analysis

Introduction: Chemotherapy-induced neutropenia (CIN) and its severe complication, febrile neutropenia, remain major challenges in oncology. Although granulocyte colony-stimulating factors (GCSFs) have reduced the incidence of these complications, limitations related to dosing schedules, polyethylene glycol (PEG)-associated concerns, and pharmacokinetic variability persist. Efbemalenograstim alfa (F-627) is a novel non-PEGylated Fc-fusion G-CSF designed for once-per-cycle administration. This systematic review and meta-analysis evaluated the efficacy and safety of efbemalenograstim alfa compared with placebo or standard G-CSFs in patients at risk of chemotherapy-induced neutropenia. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD42024628001). MEDLINE, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to 22 October 2025. Randomized controlled trials evaluating efbemalenograstim alfa in patients receiving myelotoxic chemotherapy were included. Efficacy outcomes included duration of severe neutropenia (DSN), incidence of severe neutropenia (ISN), and depth of absolute neutrophil count (ANC) nadir. Safety outcomes included adverse events, serious adverse events, and treatment discontinuations. Random-effects meta-analyses were performed. Results: Five randomized controlled trials involving approximately 800 patients with breast cancer receiving myelotoxic chemotherapy were included. Compared with placebo or standard GCSFs, efbemalenograstim alfa demonstrated comparable efficacy in reducing DSN during the first chemotherapy cycle (MD −0.32 days; 95% CI −0.79 to 0.14) and ISN (RR 0.86; 95% CI 0.73–1.03). A significant improvement in ANC nadir was observed (MD +0.40 ×10⁹/L; p = 0.0002). Rates of serious adverse events (RR 0.71; 95% CI 0.29–1.70), adverse events, and treatment discontinuations were comparable between groups. Heterogeneity was primarily attributable to the inclusion of a placebo-controlled study. Conclusion: Efbemalenograstim alfa demonstrated efficacy and safety comparable to currently available long-acting G-CSFs for the prevention of chemotherapy-induced neutropenia. Its Fc-fusion structure enables once-per-cycle administration without PEGylation, supporting its potential as an alternative long-acting G-CSF. Further studies are needed to evaluate long-term outcomes and real-world effectiveness.