45P - Protein biomarkers associated with organ-specific immune-related toxicity and response to management identified by proteome analysis of extracellular vesicles from plasma

Background

Immune related adverse events (IrAEs) are a growing challenge in oncology affecting an increasing number of patients and putting a large strain on patient health and hospital resources. The current availability of biomarkers is highly dependent on the affected organ and the management strategy based on consensus or experiences with non-CPI induced autoimmune disease. In this study, we apply proteome analysis of extracellular vesicles from plasma to assess and discover biomarkers with the potential to aid clinical staging and care of patients suffering from IrAEs.

Methods

Thirty-six patients with grade 3-4 IrAEs (colitis, hepatitis or nephritis) were included in the study. Blood samples were collected at hospital admittance before or early in management (At tox), after initiation of high dose immunosuppressive therapy (At management) and after management (After tox). The collected plasma samples were enriched for extracellular vesicles using a novel workflow and analyzed using liquid-chromatography tandem mass spectrometry (LC-MS/MS). The data analysis was performed in R using the Limma package.

Results

The sample workflow allowed median quantification of 2015 proteins in the plasma samples. In patients responding to prednisolone, we found significant decreases in CRP, SAA1 and SAA2 and a significant increase in MMP9 At management compared to At tox. CRP, SAA1 and SAA2 together with EPS8 and CFP was also significantly lowered After tox. By comparing the IrAE subtypes, definite proteins associated to specific toxicities could be identified including ALDOB, ASL and DXCR in hepatitis, SLC47A2 and PRPF40A in colitis and NCAPH in nephritis.

Conclusions

Biomarkers for monitoring IrAE management are needed to improve the clinical care of patients. Our study identifies several proteins that correlate to specific types of IrAEs and to response to toxicity management, thus, constituting relevant IrAE biomarker candidates.

Clinical trial identification

Regional Ethical Commitee reference number: H-21027448.

Legal entity responsible for the study

Capital Region of Denmark.

Funding

Novo Nordisk Foundation.

Disclosure

All authors have declared no conflicts of interest.