Abstract 866P
Background
In the last decade, treatment with the immune checkpoint inhibitors (ICI) anti-PD-1 and anti-CTLA-4 has improved overall survival (OS) for patients with metastatic cutaneous melanoma (CMM). However, only a subset of patients has long-term benefit from ICI. We have recently identified 43 potential prognostic/predictive proteins in an unbiased proteomics approach in plasma from patients with metastatic CMM. Increased levels of inflammation proteins were associated with shorter progression free survival (PFS) for patients receiving ICI (Karlsson et al Cancer Res. 81(9):2545-2555, 2021). However, in the unbiased proteomics analysis we only detect high-abundant plasma proteins. The aim of this study is to search for predictive biomarkers among low-abundant inflammation proteins in plasma from patients with metastatic CMM receiving anti-PD1.
Methods
Fifty-nine patients were included in the study between 2015 and 2019, 20 females and 39 males. The median age was 70 years old (range 31 – 84). All patients had metastatic CMM (21 M1a, 15 M1b, 17 M1c, 6 M1d). Anti-PD1 was first line treatment for 58/59 patients (one patient received anti-PD1 as 2nd line). Pretreatment plasma samples were analyzed using the OLINK target 96 inflammation platform.
Results
In the OLINK analysis, baseline expression of CXCL9, TNFRSF9, IL-15RA, CX3CL1 and MSP-2 were found to significantly increase with age (adjusted p-value <0.05). Higher IL8 expression was significantly associated with increasing M1 stage (adjusted p-value <0.05) and shorter OS (HR 2.51, 95% CI 1.19-5.29, p-value 0.012) but not with PFS (HR 1.51, 95% CI0.81-2.82, p-value 0.20). IL8, EN-RAGE/S100A12, IL10-RA and DNER were significantly associated with poorer OS (adjusted p-value <0.05). In addition, EN-RAGE/S100A12 expression also correlated to baseline LDH levels (normal vs elevated).
Conclusions
Our findings suggest that a panel of inflammation proteins may predict worse clinical outcome for patients with metastatic CMM receiving anti-PD1. These proteins warrant further investigation as potential additional therapeutic targets.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Karolinska University Hospital.
Funding
This work is supported by grants from the Swedish Cancer Society, Cancer Research Funds of Radiumhemmet and from the Swedish state under the agreement betweeen the Swedish government and the county councils, the ALF-agreement.
Disclosure
All authors have declared no conflicts of interest.