1124P - IL-6 as prognostic factor in adjuvant or metastatic skin cancer patients treated with immunotherapy: A deep biomarker analysis

Background

The immune checkpoint inhibitors (ICIs) revolutionized cancer therapeutic landscape and substantially improved the survival of patients (pts) with advanced malignancies, especially in skin cancer pts. IL-6 is a key inflammatory molecule secreted by M2 macrophages after polarization, mediating the progression of pancreatic and colorectal cancer. The purpose of this study is to retrospectively investigate the relationships between IL-6 and outcome in skin cancer patients treated with immunotherapy.

Methods

IL-6 levels were analyzed in two independent cohorts, in cohort 1 serum IL-6 were evaluated from 386 consecutive skin cancer pts before start ICIs. IL-6 was measured by Electrochemiluminescence immunoassays (ECLIA) from Cobas C6000 (Roche). In cohort 2 we conducted a gene profile analysis with Nanostring from PBMCs of 121 metastatic melanoma pts. All pts signed informed consent. Patient’s characteristics and treatment are listed in the table. Table: 1124P

Results

Among 507 pts, in cohort 1 lower serum IL-6 was associated with a better Progression Free Survival (PFS) 18.67 months (95% CI 16.6-20.7) versus 10.31 months (95% CI 8.5-12.0), HR = 0.45 (CI 0,3-0,5, p<0.0001); Overall Survival (OS) (27.59 months (95% CI 25.9-29.2) versus 20.12 months (95% CI 17.7-22.4), HR = 0.32 (CI 0,23-0,47, p<0.0001) and Overall Response Rate (ORR) (p<0.001). Similarly, IL-6 and previous therapy are associated with OS and PFS in multivariate analysis (p <0.01). We also confirmed the association between IL-6 and outcomes in all subgroups. In cohort 2 we observed a similar trend in pts with lower IL-6 expression. Moreover, higher IL-6 was associated to MAP3K12, EGFR, SELL, FPR1 genes.

Conclusions

We found that lower levels of both serum and gene expression of IL-6 are associated with better OS, PFS and ORR. Furthermore, IL-6 is associated to higher expression of genes relate to cell cycle, proliferation and metastasis. Further investigations are needed to get additional information.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Italian Ministry of Health (IT-MOH).

Disclosure

P.A. Ascierto: Financial Interests, Advisory Role, consultant/advisory role: Bristol Myers Squibb; Financial Interests, Other, consultant/advisory role: Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, OncoSec, Nouscom, Lunaphore, Seagen, iTeos; Financial Interests, Officer, consultant/advisory role: Medicenna, Bio-Al Health. All other authors have declared no conflicts of interest.