184P - Elevated baseline circulating IL-8 is associated with increased expression of the IMmotion myeloid gene signature (GS) in metastatic clear cell renal cell carcinoma (mRCC) patients (pts) treated with nivolumab (nivo) within the NIVOREN GETUG-AFU 26 study.

Background

Immunotherapy is standard of care in mRCC but tools for patients’ selection are lacking. The NIVOREN GETUG-AFU 26 study of nivolumab in mRCC included a translational program with assessment of circulating cytokines. We found IL-8 to be associated with overall survival (Carril-Ajuria et al. ASCO. 2022). Here, we aimed to evaluate the association between IL-8 and the mRCC immune landscape, including both circulating and tissue-based assessments.

Methods

Out of 720 pts treated with nivo within the NIVOREN study, 353 with available cytokine quantification were included for analysis. Immunohistochemistry expression of VEGF and CD163 at the invasive margin (IM) and at the tumor core (TC) was assessed. Previously published tissue-based GS were analyzed, including IMmotion myeloid, IMmotion Teff, and JAVELIN 101 immuno. Circulating inflammatory markers included neutrophils, NLR (neutrophil lymphocyte ratio), LIPI (Lung Immune Prognostic Index, based on derived NLR>3 and LDH>upper limit of normal). The association of baseline levels of IL-8 with baseline levels of circulating inflammatory markers, and with VEGF/CD163 expression and tissue-based GS expression were analyzed.

Results

Baseline characteristics were similar to the overall trial population. Higher levels of baseline circulating IL-8 (cut-off:17.9 pg/ml) were associated with increased baseline circulating neutrophiles (p=0.046), and NLR (p=0.008) as well as with LIPI (p=0.005). Among 353 pts, only 64 had available information on GS expression. Baseline IL-8 significantly correlated with increased IMmotion myeloid expression (p=0.041). No significant correlations between baseline circulating IL-8 and the other two GS, VEGF or CD163 expression were observed.

Conclusions

In our study, elevated baseline circulating IL-8 was not only significantly associated with higher levels of other circulating inflammatory markers, but also with increased expression of the myeloid inflammation gene signature at tumor level in mRCC pts.

Clinical trial identification

NCT03013335.

Legal entity responsible for the study

Unicancer.

Funding

Institut National du Cancer and Bristol Myers Squibb.

Disclosure

Y. Vano: Financial Interests, Personal, Invited Speaker: Ipsen, BMS, MSD, Pfizer, Merck; Financial Interests, Personal, Other, Congress and travel funding: Ipsen, MSD, Pfizer; Financial Interests, Institutional, Funding, Funding support for the CABIR study: Ipsen; Financial Interests, Institutional, Funding, Funding support for the BIONIKK study: Bristol Myers Squibb; Financial Interests, Personal, Steering Committee Member, Member of the scientific committee of the WITNESS study: Bristol Myers Squibb. B. Beuselinck: Financial Interests, Institutional, Advisory Board, Advisory board: BMS, MSD, AstraZeneca, Ipsen; Financial Interests, Institutional, Advisory Board, Testimony: BMS, MSD; Financial Interests, Institutional, Invited Speaker, Conference: Merck, Pfizer, Ipsen; Financial Interests, Institutional, Research Grant, Research grant for transational research on kidney cancer: BMS. L. Albiges: Financial Interests, Institutional, Other, Consulting: Astellas, BMS, Eisai, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche, Merck; Financial Interests, Personal, Other, Honoraria: Novartis; Non-Financial Interests, Personal, Principal Investigator, Clinical trial steering committee: Pfizer, BMS, AVEO, AstraZeneca, MSD; Non-Financial Interests, Personal, Principal Investigator: Ipsen; Non-Financial Interests, Personal, Other, Clinical trial steering committee: Roche, Exelixis; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Other, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Personal, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology (EAU). All other authors have declared no conflicts of interest.