Predictive value of ENLIGHT-DP in patients with metastatic lung adenocarcinoma treated with immune checkpoint inhibitors and platinum chemotherapy directly from histopathology slides using inferred transcriptomics

Johnathan Arnon, Gal Dinstag, Omer Tirosh, Leon Gugel, Yaron Kinar, Tzivia Gottlieb, Anna Elia, Yakir Rottenberg, Hovav Nechushtan, Michael Tabi, Philip Blumenfeld, Eli Pikarsky, Tuvik Beker, Ranit Aharonov & Aron Popovtzer

January 2025

Immune checkpoint inhibitors (ICI) have improved outcomes in non-small cell lung cancer (NSCLC). Nevertheless, the clinical benefit of ICI as monotherapy or in combination with chemotherapy remains widely varied and existing biomarkers have limited predictive value. This paper describes a blinded analysis of ENLIGHT-DP in 50 patients with lung adenocarcinoma (LUAD) treated with ICI and platinum-based chemotherapy. We show that ENLIGHT-DP is predictive of response to treatment, outperforming both TMB and PD-L1 expression, and is the only biomarker in this cohort significantly correlated with progression-free survival. ENLIGHT-DP was also highly predictive in PD-L1<1% and TMB-low outlier groups, demonstrating its potential in identifying responders among populations considered non-responsive as a whole.

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