Abstract 18P
Background
Previous studies developed predictive biomarkers related to immune checkpoint inihibitors (ICI) based on clinical trials cohorts. Here, we leverage the ORIEN data conducted under the Total Cancer Care protocol across 18 collaborating cancer centers to evaluate the predictive value of published gene expression signatures in real-world data (RWD) of patients with cancer treated with ICI.
Methods
Overall Survival (OS) was the primary endpoint. RNA-seq performed on tumors was aligned to human reference genome (GRCh38) following RSEM pipeline. Gene expressions were quantified as TPM and log2(TPM+1) transformed. 28 published predictive gene expression signatures were collected and evaluated in our cohort (Table). Mann-Whitney U-test was used to compute the difference between groups, and Kaplan-Meier survival analysis was performed. Test with p<0.05 was considered statistically significant.
Results
659 patients treated with ICI for kidney cancer (n = 151), lung cancer (n = 138), melanoma (n = 123), head and neck cancer (n = 121), sarcoma (n = 78) and bladder cancer (n = 48) were included. We defined “good” and “poor” outcomes if OS was >24 or <24 months, respectively. Twelve immune active gene signatures were associated with ICI responses in melanoma (p < 0.05); Table. An angiogenesis signature (p = 0.0281) and a tertiary lymphoid structure signature (p= 0.0133) were associated with ICI responses in kidney cancer and head and neck cancer, respectively. None of the 28 evaluated gene signatures were associated with ICI responses in lung cancer, bladder cancer or sarcoma.
Conclusions
We validated the predictive value of immune related gene signatures in melanoma, kidney, head and neck cancers utilizing RWD. Ongoing analyses are taking on a discovery approach for predictive genes and related pathways to better understand the underlying mechanisms related to tumor immunogenicity across the different tumor types. Table: 18P
Gene expression signatures and correlation with survival (>24 vs. <24 months)
| Gene Signature | Reference | P-value | Cancer |
| Tertiary Lymphoid Str. | Cabrita 2020 | 0.0133 | Head & neck |
| Angiogenesis | Cristescu 2022 | 0.0281 | Kidney |
| IFNg/Effector T cell | Fehrenbacher 2016 | 0.001 | Melanoma |
| Effector T cell | Bolen 2011 | 0.0013 | |
| IFNg-6 | Ayers 2017 | 0.0017 | |
| Immune Cytolytic Activity | Rooney 2015 | 0.002 | |
| IFNg-18 | Ayers 2017 | 0.0035 | |
| TIP Hot | Wang 2021 | 0.004 | |
| Cytotoxic Immune Signature | Davoli 2017 | 0.0047 | |
| Tertiary Lymphoid Str. | Chaurio 2022 | 0.0061 | |
| Chemokine | Coppola 2011, Mule 2012 | 0.0073 | |
| T & B cell interplay | Tarhini 2017 | 0.0114 | |
| Roh Immune Score | Roh 2017 | 0.0127 | |
| MHC-II | Liu 2021 | 0.0180 |
Clinical trial identification
NCT03977402.
Legal entity responsible for the study
Oncology Research Information Exchange Network (ORIEN) and M2GEN.
Funding
Oncology Research Information Exchange Network (ORIEN), M2GEN, Community Foundation of Tampa Bay.
Disclosure
A.A. Tarhini: Financial Interests, Personal, Advisory Board: Bristol Myers Squib, Genentech/Roche, Easai, Instil Bio, Clinigen, Regeneron, Sanofi-Genzyme, Novartis, Partner Therapeutics, BioNTech, Merck; Financial Interests, Personal and Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Genentech-Roche, Nektar, Checkmate, InflaRx; Financial Interests, Institutional, Research Grant: Regeneron, Sanofi-Genzyme, Clinigen, Acrotech, Pfizer, OncoSec. M.L. Churchman: Financial Interests, Institutional, Full or part-time Employment: M2GEN. W.S. Dalton: Financial Interests, Personal, Full or part-time Employment: M2GEN. All other authors have declared no conflicts of interest.