24P - Blood DNA methylation profiles in NSCLC patients treated with immune checkpoint inhibitors

Background

Epigenome-wide association studies showed association of the peripheral blood methylation profile with potential immunological aspects such as systemic inflammation in various diseases. Since inflammation is recognized as hallmark in cancer development and progression, DNA methylation profiles of peripheral blood cells may serve as a personalized biomarker in oncology. Here, we aim to explore if the blood DNA methylation signature changes over time in patients with NSCLC treated with immune checkpoint inhibitors.

Methods

Patients diagnosed with treatment-naive metastatic NSCLC at our institution between March 2019 and December 2023 were included. Leukocyte DNA was collected and isolated prior to treatment initiation (BL) and at first restaging (1FU). Methylation analysis was performed with Infinium Methylation EPICv2.0 microarrays. Treatment response was analyzed by a board-certified radiologist according to iRECIST 1.1 and RANO 1.0 criteria.

Results

Forty-one patients (63% males, 37% females; median age 64 years, range 45-83) were analyzed: 32/41 (78%) adenocarcinoma, 6/41 (15%) squamous cell carcinoma, 2/41 (5%) adenosquamous and 1/41 (2%) pleomorphic carcinoma. Chemoimmunotherapy was administered in 31/41 (75.6%) and ICI monotherapy in 10/42 (24.4%) patients. Except one patient who received atezolizumab (PDL-1) all other received pembrolizumab (98%, PD-1). Median days between BL and 1FU was 63 (range 38-214) or 3 cycles of ICI (range 1-6). Of the included patients, 15/41 (36.6%) were classified as responder (iCR or iPR) and 26/41 (63.4%) as non-responder (iSD or iCPD) at first restaging. Durable clinical benefit (disease control > 6 months) was achieved in 28/41 (68.3%) patients. Based on the 500 most differentially methylated CpG sites in their blood DNA methylation profiles we could not demonstrate differences between BL and 1FU.

Conclusions

In our analysis, the blood methylation profile of patients with NSCLC was stable between baseline and follow up, implying that the blood DNA methylation profile is a stabile biomarker not influenced by therapy. Further analysis of the correlation with treatment response are currently ongoing.

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

M. Preusser: Financial Interests, Personal and Institutional, Advisory Board: Bayer, Bristol Myers Squibb, Novartis, Lehrman Group (GLG), CMC Contrast, GSK, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, Boehringer Ingelheim, Telix Medscape, OncLive; Financial Interests, Personal and Institutional, Advisory Role: Gerson. 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.