...tumor infiltrating lymphocytes in patients whose tumors have a low PD_L1 expression`Immune biomarkers`infiltrating T cells that upregulate PD-1`inhibitory receptors such as TIM-3, LAG-3 and TIGIT`type of cells being positive for PD-L1(neoplastic cells vs infiltrating immune cells)`presence and phenotype of tumor-infiltrating lymphocytes in the pre-therapy lesions of patients with low expression of PD-L1`levels of CD3+, CD4+, CD8+ lymphocytes`expression, in TIL, of markers of functional differentiation to cytolytic stage such as granzyme B and TIA-1, or maturation to memory stage (CD45RO)`expression of PD1+ by TIL`expression of PD-L1 on neoplastic cells vs immune cells`expression of inhibitory receptors as LAG-3, TIM-3 and TIGIT`frequency of FOXP3+ lymphocytes, as well as of CD11b+ CD33+ MDSCs, in pre-therapy lesions...

...PD-L1 low or negative expression (tumor proportion score [TPS] < 50%) 3....

This study aims to retrospectively compare the treatment efficacy of first-line chemoimmunotherapy and chemotherapy alone in NSCLC patients with low PD-L1 expression....Patients who received chemoimmunotherapy demonstrated a significantly longer median PFS of 7.3 months (interquartile range [IQR] 5.1-13.3) compared to patients who received chemotherapy alone (4.9 months, IQR 2.5-7.9) (p = 0.015). The implementation of chemoimmunotherapy was also confirmed as independent good prognostic factor for both PFS and OS.

After 5 years of follow-up, pembrolizumab plus chemotherapy provided clinically meaningful improvements in survival outcomes and durable long-term clinical benefit versus chemotherapy alone with manageable safety in metastatic NSCLC with PD-L1 TPS <1%. These results continue to support the use of pembrolizumab plus chemotherapy as a standard of care first-line therapy for metastatic NSCLC, including in tumors with PD-L1 TPS <1%.

...For patients with tumor PD-(L)1 expression <50%, there was also a statistically significant rwOS benefit for those who received treatment, either with combination pembrolizumab plus chemotherapy (adjusted HR = 0.39, 95% CI = 0.32–0.46) or pembrolizumab monotherapy (adjusted HR = 0.55, 95% CI = 0.41–0.70),...

...For patients with tumor PD-(L)1 expression <50%, there was also a statistically significant rwOS benefit for those who received treatment, either with combination pembrolizumab plus chemotherapy (adjusted HR = 0.39, 95% CI = 0.32–0.46) or pembrolizumab monotherapy (adjusted HR = 0.55, 95% CI = 0.41–0.70),...

An exploratory analysis revealed that for patients with low PD-L1 expression, the median PFS was 4.6 vs 20.8 months for pembrolizumab with and without RT, respectively (p=0.004).