Contribution of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) use in current cancer treatment: review of clinical data

Gunzer, K.; Clarisse, Bénédicte; Lheureux, Stéphanie; Delcambre, Corinne; Joly, Florence

doi:10.1517/14712591003689964

Cited by 10 publications

(4 citation statements)

References 69 publications

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“…We queried all identified candidate proteins in the Open Targets database 56 to identify repurposing opportunities for COVID-19. While none of the proteins had already been approved drugs or drugs in clinical trials, recombinant human G-CSF (rhG-CSF), such as filgrastim and lenograstim, is used to treat the neutropenia caused by chemotherapy to stimulate the production of granulocytes from the bone marrow 57 . In line with this, phenotypic associations identified in a phenome-wide colocalisation analysis at CSF3 (±500 kb, encoding G-CSF) provided robust evidence for a shared genetic signal between plasma G-CSF and granulocyte and other white blood cell counts 58 , with consistent positive associations across candidate genetic variants (Fig.…”

Section: Resultsmentioning

confidence: 99%

ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19

et al. 2022

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Despite two years of intense global research activity, host genetic factors that predispose to a poorer prognosis of COVID-19 infection remain poorly understood. Here, we prioritise eight robust (e.g., ELF5) or suggestive but unreported (e.g., RAB2A) candidate protein mediators of COVID-19 outcomes by integrating results from the COVID-19 Host Genetics Initiative with population-based plasma proteomics using statistical colocalisation. The transcription factor ELF5 (ELF5) shows robust and directionally consistent associations across different outcome definitions, including a >4-fold higher risk (odds ratio: 4.88; 95%-CI: 2.47–9.63; p-value < 5.0 × 10−6) for severe COVID-19 per 1 s.d. higher genetically predicted plasma ELF5. We show that ELF5 is specifically expressed in epithelial cells of the respiratory system, such as secretory and alveolar type 2 cells, using single-cell RNA sequencing and immunohistochemistry. These cells are also likely targets of SARS-CoV-2 by colocalisation with key host factors, including ACE2 and TMPRSS2. In summary, large-scale human genetic studies together with gene expression at single-cell resolution highlight ELF5 as a risk gene for severe COVID-19, supporting a role of epithelial cells of the respiratory system in the adverse host response to SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19

et al. 2022

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“…We queried all identified candidate genes in the Open Targets database 45 to identify repurposing opportunities for COVID-19. While none of the genes had already approved drugs or drugs in clinical trials, recombinant human G-CSF (rhG-CSF), such as filgrastim and lenograstim, is used to treat neutropenia caused by chemotherapy to stimulate production of granulocytes from the bone marrow 46 . In line with this, phenotypic associations identified in a phenome-wide analysis of the lead cis-pQTL for G-CSF showed that genetically higher plasma G-CSF was positively associated with granulocyte and other white blood cell counts ( Fig.…”

Section: Resultsmentioning

confidence: 99%

ELF5 is a respiratory epithelial cell-specific risk gene for severe COVID-19

Pietzner

Chua

Wheeler

et al. 2022

Preprint

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Despite two years of intense global research activity, host genetic factors that predispose to a poorer prognosis and severe course of COVID-19 infection remain poorly understood. Here, we identified eight candidate protein mediators of COVID-19 outcomes by establishing a shared genetic architecture at protein-coding loci using large-scale human genetic studies. The transcription factor ELF5 (ELF5) showed robust and directionally consistent associations across different outcome definitions, including a >4-fold higher risk (odds ratio: 4.85; 95%-CI: 2.65-8.89; p-value<3.1x10-7) for severe COVID-19 per 1 s.d. higher genetically predicted plasma ELF5. We show that ELF5 is specifically expressed in epithelial cells of the respiratory system, such as secretory and alveolar type 2 cells, using single-cell RNA sequencing and immunohistochemistry. These cells are also likely targets of SARS-CoV-2 by colocalisation with key host factors, including ACE2 and TMPRSS2. We also observed a 25% reduced risk of severe COVID-19 per 1 s.d. higher genetically predicted plasma G-CSF, a finding corroborated by a clinical trial of recombinant human G-CSF in COVID-19 patients with lymphopenia reporting a lower number of patients developing critical illness and death. In summary, large-scale human genetic studies together with gene expression at single-cell resolution highlight ELF5 as a novel risk gene for COVID-19 prognosis, supporting a role of epithelial cells of the respiratory system in the adverse host response to SARS-CoV-2.

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“…The main reason is that the drug prices of the short-acting G-CSFs are quite similar in Taiwan; in addition, a more effective prophylactic benefit of lenograstim was assumed in the model based on the NHIRD analysis. Nevertheless, previous clinical trials have demonstrated that the efficacy of lenograstim in reducing the incidence of FN is similar to that of filgrastim [ 43 ]. In reality, there is generally only one short-acting drug available in a hospital.…”

Section: Discussionmentioning

confidence: 99%

Cost-effectiveness analysis of granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced febrile neutropenia in patients with breast cancer in Taiwan

Tseng,

Chiang,

Hsu

et al. 2024

PLoS ONE

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Objectives To examine the cost-effectiveness of using granulocyte colony-stimulating factor (G-CSF) for primary or secondary prophylaxis in patients with breast cancer from the perspective of Taiwan’s National Health Insurance Administration. Methods A Markov model was constructed to simulate the events that may occur during and after a high-risk chemotherapy treatment. Various G-CSF prophylaxis strategies and medications were compared in the model. Effectiveness data were derived from the literature and an analysis of the National Health Insurance Research Database (NHIRD). Cost data were obtained from a published NHIRD study, and health utility values were also obtained from the literature. Sensitivity analyses were performed to assess the uncertainty of the cost-effectiveness results. Results In the base-case analysis, primary prophylaxis with pegfilgrastim had an incremental cost-effectiveness ratio (ICER) of NT$269,683 per quality-adjusted life year (QALY) gained compared to primary prophylaxis with lenograstim. The ICER for primary prophylaxis with lenograstim versus no G-CSF prophylaxis was NT$61,995 per QALY gained. The results were most sensitive to variations in relative risk of febrile neutropenia (FN) for pegfilgrastim versus no G-CSF prophylaxis. Furthermore, in the probabilistic sensitivity analysis, at a willingness-to-pay threshold of one times Taiwan’s gross domestic product per capita, the probability of being cost-effective was 88.1% for primary prophylaxis with pegfilgrastim. Conclusions Our study suggests that primary prophylaxis with either short- or long-acting G-CSF could be considered cost-effective for FN prevention in breast cancer patients receiving high-risk regimens.

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Contribution of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) use in current cancer treatment: review of clinical data

Cited by 10 publications

References 69 publications

ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19

ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19

ELF5 is a respiratory epithelial cell-specific risk gene for severe COVID-19

Cost-effectiveness analysis of granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced febrile neutropenia in patients with breast cancer in Taiwan

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