1323P Natural killer cell activity as a prognostic biomarker in non-small cell lung cancer patients treated with check-point inhibitors

Background

Immunotherapy has improved survival for patients with incurable non-small cell lung cancer (NSCLC). The only validated biomarker is tumour PD-L1 expression. The aim of the present study was to evaluate NK cell activity as a prognostic biomarker in patients with NSCLC treated with PD-1/PD-L1 inhibitors.

Methods

Enrolled patients were eligible for PD-1/PD-L1 inhibitor treatment (any line). NK cell activity was estimated using 1 ml of blood. Blood was sampled into special tubes (NK Vue® tubes) and placed in an incubator at 37°C within 15 minutes of sampling. Following 24 hours of stimulation the level of interferon gamma (IFNγ) in the plasma was measured by ELISA (NK Vue® ELISA) as a surrogate for NK cell activity. Cutpoint between high and low NK cell activity was set at IFNγ 200 pg/ml per the manufacturer’s recommendation.

Results

Blood samples were available from 78 patients before, and 73 patients after, the first cycle of treatment. There was no significant difference in IFNγ between baseline (median 158 pg/ml, interquartile range [IQR] 32.5-424 pg/ml) and after the first treatment cycle (median 154 pg/ml, IQR 32.5-500 pg/ml, p=0.697, Wilcoxon signed-rank test). In patients with high NK cell activity (IFNγ >= 200 pg/ml) after the first cycle of treatment, 21% had progressive disease at the first evaluation. This was 34% for patients with low NK cell activity (IFNγ < 200 pg/ml), but the difference did not reach statistical significance (p=0.061, Fisher’s exact test). There was no statistically significant difference in overall survival (OS) when grouping patients into high vs low NK cell activity at baseline. However, high NK cell activity after one cycle of PD-1/PD-L1 inhibitor was a favourable prognostic factor with a median overall survival (OS) of 436 days (IQR 234-597 days) compared to patients with low NK cell activity (median 216 days, IQR 143-492 days, p=0.004, Logrank test).

Conclusions

High NK cell activity after the first cycle of PD-1/PD-L1 inhibitor is a favourable prognostic factor in patients with NSCLC.

DOI: https://doi.org/10.1016/j.annonc.2020.08.1637

https://www.annalsofoncology.org/article/S0923-7534(20)41633-3/fulltext