2024 World Conference on Lung Cancer (WCLC) - Posters-P2.11B.03 Circulating Hallmarks of Hyperprogression in NSCLC upon 1st Line PD-(L)1 Inhibitors Alone or in Combination with Chemotherapy

P2.11B.03 Circulating Hallmarks of Hyperprogression in NSCLC upon 1st Line PD-(L)1 Inhibitors Alone or in Combination with Chemotherapy

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The study explores the phenomenon of hyperprogressive disease (HPD) in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) alone or in combination with chemotherapy (PCT). HPD has been associated with poor survival outcomes, and its occurrence in patients treated with ICI ranges from 14% to 26%. This research specifically investigates the role of circulating low-density neutrophils (LDNs), especially the immature CD10- subtype, as biomarkers for HPD. <br /><br />Patients receiving first-line treatment with either ICI alone or in combination with PCT at a single institution were assessed for the presence of HPD and circulating neutrophil subsets. It was found that a 30.5% cut-off value of immature CD10- LDNs could predict high HPD risk, as determined by the Youden index. In the PCT-ICI cohort of 69 patients, no HPD was reported, contrasting with 11% HPD occurrence in the single-agent ICI group.<br /><br />Interestingly, individuals at high risk for HPD showed a significant reduction (45.2%) in immature CD10- LDNs upon receiving PCT-ICI, while those under single-agent ICI had only a 2.5% decrease. In vitro experiments further demonstrated that immature CD10- LDNs are highly susceptible to necrotic cell death when treated with cisplatin, indicating that PCT might prevent HPD by promoting the death of these cells.<br /><br />Single-cell RNA sequencing revealed senescent T-cells in HPD cases, indicating that an interplay between immature neutrophils and exhausted T-cells might contribute to HPD. This suggests that patients with high levels of immature neutrophils and senescent T-cells are at greater risk for HPD and might benefit more from PCT-ICI combinations rather than ICI alone.<br /><br />The findings underscore the potential of immature CD10- LDNs as biomarkers for HPD and suggest that combining chemotherapy with immunotherapy might mitigate the risk of hyperprogression in NSCLC patients.

Asset Subtitle

Roberto Ferrara

Meta Tag

Speaker Roberto Ferrara

Topic Metastatic NSCLC – Immunotherapy

Keywords

hyperprogressive disease

non-small cell lung cancer

immune checkpoint inhibitors

chemotherapy

circulating low-density neutrophils

immature CD10- subtype

biomarkers

senescent T-cells

single-cell RNA sequencing

cisplatin