TMB, genetic alterations and PD-L1 expression in non-small cell lung cancer

<bold>Background:</bold> High programmed death–ligand 1 (PD-L1) and tumour mutation burden (TMB) are associated with superior benefit in NSCLC immunotherapy. Recent studies demonstrate, that oncogenic alterations also play critical role in the response to immune checkpoint inhibitors. <bold>Methods:</bold> 44 specimens from advanced NSCLC without EGFR mutations were collected. PD-L1 expression was assessed by tumour proportion score (TPS) and tissue-based next-generation sequencing was performed by FoundationOne CDx assay. <bold>Results:</bold> Tumour tissue was positive for PD-L1 in 64% cases. TPS <1%, 1-49% and ≥50% was in 36%, 27% and 36% cases. High TMB (≥10 mut/Mb) was in 37% cases. There was no association between PD-L1 and TMB. Targetable mutations were seen in 20.45% cases: EGFR 2.3%, ERBB2 2.3%, KRAS (G12C) 2.3%, MET 2.3%, RET 2.3%, ALK 4.5%, and ROS1 4.5%. Other most often detected mutations: TP53 54.5%, CDKN2A/B 52.3%, KRAS 34.1%, MTAP 31.8% and STK11 18.2%. TERC amplification was associated with higher age (<italic>p</italic>=0.022), FGFR1 amplification and TP53 mutation – with higher number of pack-years (<italic>p</italic>=0.037, <italic>p</italic>=0.005). The probability to detect ROS1 mutation was higher in female (<italic>p</italic>=0.048). KEAP1 mutation was more likely to be detected in PD-L1 negative tumours (<italic>p</italic>=0.013). TP53 mutation was associated with higher PD-L1 expression (<italic>p</italic>=0.017) and higher TMB count (<italic>p</italic>=0.026). ZNF703 amplification was more often detected in TMB high tumours (<italic>p</italic>=0.046), while ALK and CDKN2A/B mutation – in TMB low tumours (<italic>p</italic>=0.021, <italic>p</italic>=0.049). <bold>Conclusion:</bold> TMB ≥10 mut/Mb was detected in 1/3 and PD-L1 TPS ≥1% in 2/3 of cases. Targetable mutations were seen in 1/5 of cases. Some significant associations between TMB, PD-L1 expression and molecular alterations were found.