1451P - Identifying long-term responders to immune checkpoint blockade: Potential utility of serum proteomic profiling in metastatic non-small cell lung cancer

Background

Immune checkpoint blockade (ICB) has significantly impacted the treatment landscape in non-small cell lung cancer (NSCLC). However, this benefit is restricted to a subset of patients. While these results are encouraging, it is crucial to identify those patients who benefit the most from ICB and those who are refractory. Here we investigate the potential utility of longitudinal serum proteomic profiling to identify predictive biomarkers.

Methods

We included 40 metastatic NSCLC patients who received ICB treatment at Hospital del Mar, Barcelona between 2017-2021. Patients were categorized as long-term responders (LTR, n=20) if they had maintained radiologic response for more than 2 years or non-responders (NR, n=20) if they had disease progression at first radiological evaluation. Serum protein levels were assessed longitudinally (before treatment, previous cycle 2) using the Olink® Explore 384 Oncology panel.

Results

LTR had a greater proportion of high PD-L1 expression (p=0.01). Analysis of baseline serum samples showed an increase in LTR of proteins levels related to apoptosis and autophagy (CASP8, ATG4A), TCR signaling pathway (STAT5B, CRACR2A) and myeloid differentiation (ZBTB16, ARG1) (p<0.05 for all proteins). Higher levels of proteins related to immunosuppression and tumorigenesis (PDCD1, TGFBR2, KLK4, KLK6) prior to the second cycle of ICB were associated with poorer response to ICB, with non-responders exhibiting significantly higher levels (p<0.05 for all). Gene set enrichment analysis showed that LTR had an increase in myeloid cell differentiation process, while higher levels of immunoregulatory interactions between lymphoid and non-lymphoid cells were observed in NR (p<0.001 for all).

Conclusions

Our findings suggest that patients with high levels of proteins related to apoptosis, autophagy, TCR signaling, and myeloid differentiation at baseline may identify LTR to ICB. Our study underscores the potential use of baseline and longitudinal assessment of serum proteomics as valuable tools for patient selection who are suitable candidates for ICB. Further studies are needed to validate these findings and establish their potential clinical utility.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

B. Bellosillo Paricio: Financial Interests, Personal, Research Grant: Thermo Fisher, Roche Diagnostics, Roche Pharma, AstraZeneca; Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Janssen, Novartis; Financial Interests, Personal, Speaker’s Bureau: Janssen, Merck-Serono, Novartis, Qiagen, Thermo Fisher, Pfizer, Bristol Myers Squibb. E. Arriola: Financial Interests, Personal, Advisory Board: Roche, Boehringer Ingelheim, Lilly; Financial Interests, Personal, Invited Speaker: Takeda, MSD, AstraZeneca, BMS, Thermo Fisher Scientific, Guardant Health, Pfizer; Financial Interests, Personal, Other, Co-founder: Trialing Health; Financial Interests, Institutional, Research Grant: AstraZeneca. All other authors have declared no conflicts of interest.