Lipegfilgrastim for primary prophylaxis of febrile neutropenia in patients treated for advanced-stage classical hodgkin lymphoma: successful outcomes from a multicenter cohort study

In patients with classical Hodgkin lymphoma (c-HL) undergoing ABVD chemotherapy for advanced disease, the optimal strategy to prevent febrile neutropenia (FN)—defined as fever ≥ 38 °C with absolute neutrophil count (ANC) < 1000/mm³—remains debated. Possible prophylaxis approaches include: i) secondary prophylaxis with on-demand granulocyte colony-stimulating factor (G-CSF, filgrastim), ii) primary prophylaxis with filgrastim, or iii) primary prophylaxis with long-acting G-CSF formulations such as pegylated or glyco-pegylated G-CSF (lipegfilgrastim). We conducted a multicenter retrospective cohort study from 2010 to 2024 involving 450 untreated c-HL patients (Ann Arbor stage IIB-IV) scheduled for six ABVD cycles, divided into three five-year periods, each with a different G-CSF prophylaxis strategy. From 2010 to 2014, 131 patients received on-demand filgrastim when ANC ≤ 1 × 10^9/L (on-demand- group); from 2015 to 2019, 152 patients systematically received filgrastim six times per cycle (filgrastim-group); from 2020 to 2024, 167 patients received lipegfilgrastim twice per cycle as primary prophylaxis (lipegfilgrastim-group). A total of 85 neutropenia episodes occurred: 52 in the on-demand-group, 30 in the filgrastim-group, and 3 in the lipegfilgrastim-group (P < 0.001); FN incidence was 24%, 14%, and 2%, respectively (P < 0.0001). Chemotherapy disruptions due to FN were 14%, 6%, and 1%, respectively (P < 0.001). Grade 3 bone pain occurred in 5% of patients and was managed with analgesics. Primary prophylaxis with lipegfilgrastim significantly reduced FN rates, hospitalizations, and chemotherapy interruptions in patients with advanced-stage c-HL treated with ABVD, demonstrating improved tolerability of chemotherapy.