Abstract 1070P
Background
ICBs revolutionized the treatment of advanced NSCLC patients but only a fraction of them obtain a response and clinical benefit from ICBs is often difficult to predict. Viral infections, whether acute, chronic or latent, have an impact on the immune system but their effect on ICBs efficacy is unknown. The aim of our study is to unveil the potential implications of antibody response to previous viral infections in predicting the response to ICBs in NSCLC patients.
Methods
Sera from patients enrolled in the prospective PREMIS and MSN studies were analyzed with VirScan (CDI Labs, US), a high-throughput method that comprehensively analyzes epitope-level antiviral IgG antibodies via programmable phage display and immunoprecipitation sequencing (PhIP-Seq). The library contains ∼100,000 clones displayed as 56-residue peptides, with a 28-residue overlap, spanning the reference protein sequences of all viruses with known human tropism in the UniProt database collapsed to 95% sequence similarity. 3 L2-penalized logistic regression models were trained with a 10x10-fold cross-validation to predict 6-month PFS to ICBs from (i) known predictive clinical variables, (ii) VirScan peptides, and (iii) a combination of both. Statistical significances were computed with the resampled t-test corrected for training set dependencies in cross-validation.
Results
129 patients treated with ICBs alone (45 1st line, 70 2nd line, 14 3rd or later), 66 with ICB in combination with chemotherapy and 61 with chemotherapy alone were included. A signature based only on the peptides showed an AUC of 0.657 in predicting PFS > 6 months vs 0.708 for a model including only clinical variables (sex, age, ECOG PS, site of metastasis, histology, derived neutrophil/lymphocytes, LDH, PD-L1) and 0.752 combining clinical data and VirsScan results (p < 0.001 vs the clinical only model). The viral signature was shown significantly less predictive for the chemo-immunotherapy (AUC 0.437) and the chemotherapy (AUC 0.529) groups compared to the ICBs group (p < 0.001 for both).
Conclusions
Previous viral infections as assessed by VirScan may have a role in predicting the response to ICBs in NSCLC patients.
Clinical trial identification
PREMIS: NCT 03984318; MSN: NCT02105168.
Editorial acknowledgement
Legal entity responsible for the study
Institut Gustave Roussy.
Funding
Fondation Dassault.
Disclosure
G. Roman: Financial Interests, Personal, Full or part-time Employment: CDI laboratories. N. Chaput-Gras: Financial Interests, Personal, Advisory Board, Strong-Iopredi Scientific Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Educational Session on Immune Cell Death: Servier; Financial Interests, Institutional, Expert Testimony, Expertise on Immune Cell Death Biomarkers: Servier; Financial Interests, Personal, Invited Speaker: Cytune Pharma; Financial Interests, Institutional, Research Grant, Research grant to identify immune biomarkers associated to clinical response in patients treated with agonistic mAbs: GSK; Financial Interests, Institutional, Research Grant, Preclinical studies in mice: GSK; Financial Interests, Institutional, Research Grant, Immune profiling of Head & Neck tumors: Sanofi. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. F. Barlesi: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis, Seattle Genetics, Takeda; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd. T. Hulett: Financial Interests, Personal, Full or part-time Employment: CDI laboratories. A. Marabelle: Non-Financial Interests, Funding: Roche/Genentech; BMS, MSD, Pfizer, Lytix Pharma, Eisai, AstraZeneca/MedImmune, Tesaro, Chugai, GSK, Novartis, Bayer. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, EISAI, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. All other authors have declared no conflicts of interest.