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Background: PD-1/PD-L1 inhibitors have improved survival for patients with non-small cell lung cancer (NSCLC). We evaluated natural killer cell activity (NKA) and methylated HOXA9 circulating tumor DNA (ctDNA) as prognostic biomarkers in NSCLC patients treated with PD-1/PD-L1 inhibitors. Methods: Plasma was prospectively collected from 71 NSCLC patients before treatment with PD-1/PD-L1 inhibitors and before cycles 2–4. We used the NK Vue® assay to measure the level of interferon gamma (IFNγ) as a surrogate for NKA. Methylated HOXA9 was measured by droplet digital PCR. Results: A score combining NKA and ctDNA status measured after one treatment cycle had a strong prognostic impact. Group 1 had IFNγ < 250 pg/ml and detectable ctDNA (n = 27), group 2 consisted of patients with either low levels of IFNγ and undetectable ctDNA or high levels of IFNγ and detectable ctDNA (n = 29), group 3 had IFNγ ≥250 pg/ml and undetectable ctDNA (n = 15). Median OS was 221 days (95% CI 121–539 days), 419 days (95% CI 235–650 days), and 1158 days (95% CI 250 days—not reached), respectively (P = 0.002). Group 1 had a poor prognosis with a hazard ratio of 5.560 (95% CI 2.359–13.101, n = 71, P < 0.001) adjusting for PD-L1 status, histology, and performance status. Conclusions: Combining NKA and ctDNA status after one cycle of treatment was prognostic in patients with NSCLC treated with PD-1/PD-L1 inhibitors.
Bibliographical notePublisher Copyright:
© 2023, The Author(s).
- B7-H1 Antigen/genetics
- Biomarkers, Tumor/genetics
- Carcinoma, Non-Small-Cell Lung/drug therapy
- Immune Checkpoint Inhibitors/pharmacology
- Killer Cells, Natural/metabolism
- Lung Neoplasms/drug therapy
- Programmed Cell Death 1 Receptor
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- 1 Conference presentations
NK cell activity and methylated HOXA9 circulating tumor DNA as prognostic biomarkers in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.
Sara Witting Christensen Wen (Guest lecturer)3. Jun 2022
Activity: Talks and presentations › Conference presentations