NK cell activity and methylated HOXA9 ctDNA as prognostic biomarkers in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitors
Menée à partir d'échantillons plasmatiques prélevés sur 71 patients atteints d'un cancer du poumon non à petites cellules traité par inhibiteurs de PD-1/PD-L1, cette étude met en évidence l'intérêt, pour établir un pronostic, d'un système de score combinant l'activité des cellules NK (mesurée par le niveau de l'interféron gamma) et le statut de méthylation de la région du promoteur du gène HOXA9 situé sur l'ADN tumoral circulant
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 (IFN
γ) 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 IFN
γ and undetectable ctDNA or high levels of IFNγ and detectable ctDNA (n
= 29), group 3 had IFN
γ
≥
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.
British Journal of Cancer , article en libre accès, 2023