Lipegfilgrastim 6mg/0.6ml solution for injection pre-filled syringes

Wang et al. recently published a systematic review and metaanalysis on the impact of primary prophylaxis (PP) with granulocyte colony-stimulating factors (G-CSF) on febrile neutropenia (FN) during chemotherapy [1]. In the article, the authors state that Bover all chemotherapy cycles, there was a numerical but statistically nonsignificant increase in the FN risk for lipegfilgrastim PP versus pegfilgrastim PP^ four times. We would like to state that in our view, this claim is not justified for the following three major reasons:

Abstract licence: CC BY-NC 4.0

Chemotherapy, irradiation, and other agents are widely used to target the process of cell division in neoplastic cells. However, while these therapies are effective against most cancers, the high proliferative rate of the cells of the hematopoietic system that produce billions of blood cells needed daily throughout life is extremely sensitive to these agents, resulting in loss of blood cell populations, which can be life threatening. Neutropenia is the most serious hematologic toxicity of chemotherapy, which can result in patient morbidity and mortality due to opportunistic infection and often is the limiting factor in dose escalation or duration of chemotherapeutic administration. Neutropenic patients often require hospitalization and incur substantial medical costs associated with anti-infective therapy. Treatment of iatrogenic and congenic neutropenia was changed in the early 1990s with the introduction of filgrastim (Neupogen®) and pegfilgrastim (Neulasta®). With the expiration of patent lives of both of these drugs, biosimilars have begun to emerge. In this review, we will summarize the chemical characteristics, pharmacokinetics, safety and efficacy of lipegfilgrastim (Lonquex®), the first long-acting biosimilar filgrastim to receive regulatory approval and enter the marketplace.

Abstract licence: CC BY-NC 3.0

Abstract Febrile neutropenia (FN) is one of the most important clinical signs of infection, especially for older patients with indolent B cell non-Hodgkin lymphomas (iBC-NHLs) receiving frontline immune-chemotherapy with bendamustine-rituximab (BR). Data on the optimal strategy for infection prophylaxis from the start of chemotherapy until 1 month after the last cycle is scanty in this setting of patients, and for this reason, we carried out a multicentric retrospective study on vigorous primary anti-infectious prophylaxis consisting of lipegfilgrastim, trimethoprim-sulfamethoxazole, and acyclovir. From January 2017 to January 2022, 200 patients met the inclusion criteria and were enrolled in the final analysis. As per the primary endpoint, during the immune-chemotherapy period, the overall incidence of FN was 6% consisting of fever of unknown origin (2%), clinically documented infections (2.5%), and microbiologically documented infections (1.5%). Chemotherapy disruption for a delay of at least 1 week related to FN that required hospitalization was recorded in 1% of patients ( n  = 2). Prophylaxis was well tolerated with grade 3 toxicity (bone pain) in only 10% of patients and was successfully managed with paracetamol or tramadol. Systematic, prompt, and sustained use of vigorous primary anti-infectious prophylaxis was able to reduce the rate of fever episodes, thus averting parenteral antimicrobial administrations, hospitalizations, and immune-chemotherapy disruption.

Abstract licence: CC BY 4.0

Abstract Purpose Breast cancer is one of the most prevalent malignant diseases in women. The development of dose dense chemotherapy regimens has improved clinical outcomes but has been associated with increased hematological toxicity. Currently there is a paucity of data on the use of lipegfilgrastim in dose dense AC treatment in early breast cancer. The purpose of this study was to assess the use of lipegfilgrastim in the treatment of early breast cancer and to examine the incidence of treatment-related neutropenia during the dose dense AC phase and subsequent paclitaxel treatment. Methods This was a single arm, non-interventional, prospective study. The primary endpoint was to determine the rate of neutropenia defined as ANC of  38 °C and ANC < 1.0 × 109/L), treatment delays, premature treatment cessation and toxicity. Results Forty-one participants were included in the study. Of the 160 planned dose dense AC treatments, 157 were administered, and 95% (152/160) of these were given on time. The rate of treatment delay was 5% (95% CI 2.2 to 9.9%) due to infection (4) and mucositis (1). Four (10%) patients developed febrile neutropenia. The most frequently occurring adverse event was grade 1 bone pain. Conclusion Lipegfilgrastim is an effective option in the prophylaxis of chemotherapy-induced neutropenia, and its use in everyday anti-cancer treatment can be considered.

Abstract licence: CC BY 4.0

This study compared efficacy and safety of lipegfilgrastim with filgrastim in pediatric patients. Children and adolescents receiving chemotherapy (4 cycles) for Ewing sarcoma or rhabdomyosarcoma were randomized 1:1 to lipegfilgrastim (100 µg/kg) once per cycle or filgrastim (5 µg/kg), once daily for ≥ 5 days for up to 14 days or until absolute neutrophil count (ANC) recovery. In 39 evaluable patients, no meaningful difference was observed between lipegfilgrastim and filgrastim treatment groups in duration of severe neutropenia (DSN; mean [standard deviation]) in cycle 1 (2.7 [2.25] vs. 2.5 [2.09] days); least squares mean treatment difference (lipegfilgrastim minus filgrastim) 1.0 day (95% CI: -0.21,2.26) or cycles 2–4, duration of very severe neutropenia in cycles 1–4, incidence of severe neutropenia (85% vs. 84%) or very severe neutropenia (70% vs. 68%). The incidence of febrile neutropenia was numerically lower with lipegfilgrastim (35%) vs. filgrastim (42%). Mean area under the curve of ANC until day 15 in cycle 1 was numerically higher with lipegfilgrastim vs. filgrastim (105 × 109/L*days vs. 84 × 109/L*days). There were no meaningful differences between treatment groups, in cycles 1–4, in mean ANC nadir values, or time to ANC nadir or ANC recovery. Mean administration of lipegfilgrastim was less than filgrastim (4 vs. 31.7 times). No unexpected safety signals were observed. Lipegfilgrastim demonstrated comparable efficacy and tolerability to filgrastim in reducing duration and incidence of neutropenia. A reduced dosing frequency of once per cycle could be particularly beneficial for children, enhancing convenience and improving adherence.

Abstract licence: CC BY-NC-ND 4.0

Abstract 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.

Abstract licence: CC BY 4.0