Abstract 691P
Background
Clinically relevant biomarkers of response to anti-PD-1 therapy in R/M SCCHN are limited to PD-ligand-1 combined proportion score on tumor biopsies. This study aims to identify DNA based methylation biomarkers on easily accessible peripheral blood samples.
Methods
An ongoing prospective multi-center study is collecting peripheral blood during routine care visits from patients with R/M SCCHN receiving anti-PD-1 therapy based treatment. These samples undergo DNA isolation, bisulfite conversion, and methylation profiling using Illumina EPIC microarray. Immune profiles are subsequently derived using cell deconvolution methods developed by our group (PMID 35140201). We present results of preliminary analyses for subjects who received anti-PD-1 monotherapy, with clinical benefit (Group A) versus progression of disease or death (Group B) at 100 days from start of treatment. Logistic regression models adjusted for age and sex were used to examine the relationship between DNA methylation derived immune profiles and clinical benefit from anti-PD-1 therapy.
Results
50 patients with R/M SCCHN have been enrolled as of March 25, 2022. 42 subjects received anti-PD-1 monotherapy, 7 subjects received concurrent chemotherapy, and 1 subject received concurrent cetuximab. 26 subjects were eligible for this preliminary analysis. Mean (SD) age in groups A and B were 66.8 (10.4) and 65.7 (12.2), respectively (P=0.79). 7/8 (88%, group A) and 16/18 (89%, group B) were male. Group A had a numerically but not statistically higher CD4 naïve/ total CD4 T cell ratio (p=0.06). Group A had significantly lower myeloid derived suppressor cell scores (Odds ratio: 0.86, 95% C.I.: 0.75-0.94). Additional analyses of 18 subjects (Group A: 7, Group B: 11) with immune profiles available at Cycle 2 Day 1 showed a significant decrease in CD4 naïve T cells (p=0.005) and an increase in CD8 memory T cells (p=0.04) in Group A compared to Group B. Updated analyses will be presented at the meeting.
Conclusions
DNA-based epigenetic immune-profiling can identify early predictive markers of disease benefit with anti-PD-1 therapy in readily available peripheral blood samples.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Institutes of Health R01 CA253976.
Disclosure
J.K. Wiencke: Financial Interests, Personal, Advisory Role, Co-founder: Cellintec. L.A. Salas: Financial Interests, Personal, Other, Application number: 63/148,695: Provisional US patent application. K.T. Kelsey: Financial Interests, Personal, Advisory Role, Co-Founder: Cellintec. R. Haddad: Financial Interests, Personal, Advisory Role: Celgene, Eisai, AstraZeneca, Pfizer, Loxo, Immunomic Therapeutics, GSK, Gilead Sciences, Vaccinex, EMD Serono, BioNTech AG, Achilles Therapeutics, Bayer, Coherus Biosciences, Boehringer Ingelheim, Mirati; Financial Interests, Personal and Institutional, Advisory Role: Merck, Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Boehringer Ingelheim, Bristol Myers Squibb, Merck, Celgene, AstraZeneca, Genentech, Pfizer, Kura. All other authors have declared no conflicts of interest.