Erschienen:
American Society of Clinical Oncology (ASCO), 2020
Erschienen in:Journal of Clinical Oncology
Sprache:
Englisch
DOI:
10.1200/jco.2020.38.15_suppl.10011
ISSN:
0732-183X;
1527-7755
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p> 10011 </jats:p><jats:p> Background: Increasing evidence suggests that the B cell response in cancer patients is an important component of anti-tumour immunity. Autoantibodies targeting tumour and self-antigens may serve as biomarkers of anti-tumour and auto-immunity. As they can be measured in patient' sera, they have great potential as clinical routine biomarkers. The objective of this study was to explore if autoantibodies are associated with survival and immune related adverse events (irAE) in patients with metastatic melanoma under checkpoint inhitibor (CPI) therapy. Methods: Pre-treatment serum samples from 333 metastatic melanoma patients receiving CPI therapy at 5 European centers were retrospectively used to identify autoantibody signatures for survival and irAE. We designed a cancer immunotherapy antigen array comprising 832 autoimmune and tumour antigens as well as immune and cancer pathway proteins. Statistical tests were separately performed for patients treated with anti-CTLA4 (alone or in combination) and with anti-PD1 antibody monotherapy. Cox-regression analysis and univariate statistical tests were applied for biomarker discovery. Progression free and overall survival was measured from treatment initiation to tumor progression or death date. irAE were recorded including onset date and grade (CTC-AE). Results: For each therapy group we identified a set of autoantibody reactivities in untreated melanoma patients that were associated with the development of irAEs and/or survival. The identified autoantibodies target a diverse set of antigens comprising neoantigens (p53), cancer testis antigens (MAGEB4), paraneoplastic antigens (gephyrin), autoantigens (ribosomal proteins, Nor-90) and FGFR1. Autoantigens that correlated with irAE and survival were e.g. anti-MAGEB4 and anti-FGFR1. Elevated anti-MAGEB4 pre-treatment levels were associated with longer overall survival (p = 0.002, HR = 0.77) and the development of irAEs (p = 0.002, HR = 1.27) in ipilimumab +/- nivolumab treated patients. Higher pre-treatment anti-FGFR1 antibodies were associated with shorter survival (p = 0.008, HR = 1.27) and a lower a lower frequency of irAEs (p = 0.04, HR = 0.69) in these patients. Conclusions: We identified autoantibody targets suggesting a diverse B cell response to antigens expressed in tumours and those associated with autoimmunity. Depending on the specific antigen, the immune response towards those antigens may be associated with anti-tumour or pro-tumour responses. </jats:p>