23P - Non-small cell lung cancer DNA methylation profiles correlate with immune checkpoint inhibitor response

Background

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, robust biomarkers precisely predicting treatment response have not yet been discovered. We aimed to evaluate tumor DNA methylation signatures as a potential new biomarker for ICI response.

Methods

Patients with non-small cell lung cancer (NSCLC) receiving ICIs at two independent tertiary care centres were retrospectively identified. DNA methylation profiles of tumor tissue FFPE specimen before initiation of ICI were analysed by Infinium Methylation EPIC microarrays and bioinformatically correlated with radiological response. Responders were defined as patients with complete remission or partial remission at first restaging. Response assessment was performed by board-certified radiologist according to iRECIST v1.1.

Results

In this preliminary analysis, a total of 95 patient samples (median age: 67 years [range: 36-89 years], 53 male, 42 female, 75 adenocarcinoma, 20 squamous cell carcinoma) were included. Supervised clustering according to ICI response revealed three distinct clusters (p<0.001). Cluster 1 included only ICI non-responders (29/29), while the majority of Cluster 3 consisted of responders (11/17). In further analysis according to histological subtype, the 3 clusters were also significantly associated with ICI response in the subgroup of adenocarcinoma as 39/41 (95.1%) in Cluster 1 were non-responders and 10/10 (100%) in Cluster 3 were responders (p<0.001). In squamous cell carcinoma, only 2 methylation clusters were evident. Cluster 1 with only non-responders (14/14) and Cluster 2 with mainly responders (5/6; p<0.001).

Conclusions

Tumor tissue methylation profiling may serve as a promising biomarker to predict ICI treatment response in NSCLC patients.

Legal entity responsible for the study

The authors.

Funding

The financial support by the Austrian Federal Ministry for Digital and Economic Affairs, the National Foundation for Research, Technology and Development and the Christian Doppler Research Association is gratefully acknowledged.

Disclosure

J. Furtner: Financial Interests, Personal, Invited Speaker: Seagen, Novartis, Sanova; Financial Interests, Personal, Advisory Board: Servier. A.S. Berghoff: Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck, AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, CeCaVa, Seagen, Alexion, Servier; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Roche; Non-Financial Interests, Personal, Leadership Role, Board Member: European Association of Neuro-Oncology. All other authors have declared no conflicts of interest.