Profiling autoantibodies at baseline and during immune checkpoint inhibitor therapy of renal cell carcinoma patients-exploratory results from TITAN-RCC.

BACKGROUND

Immune checkpoint inhibitor (ICI) administration profoundly promotes T-cell-mediated antitumor effects, but also frequently causes the development of immune-related adverse events (irAEs) in cancer patients. Previous studies explored the relevance of autoantibodies as predictive biomarkers for irAE development and treatment response, leading to conflicting results. To gain novel insights, we determined the presence of autoantibodies and their predictive value in ICI-treated renal cell carcinoma (RCC) patients.

PATIENTS AND METHODS

Within the multicenter clinical trial TITAN-RCC (NCT02917772), we prospectively analyzed sera from 170 RCC patients at baseline and various time points during ICI therapy. Immunofluorescence, enzyme-linked immunosorbent assay, and chemoluminescence were applied for the detection of various autoantibody entities. Valuation of titers was defined per individual autoantibody. Statistical analysis was carried out to evaluate correlations between the presence of autoantibodies and irAEs or clinical outcome.

RESULTS

Of 170 ICI-treated RCC patients, 37% had pre-existing autoantibodies. In addition, of 107 autoantibody-negative patients at baseline, 60% showed a new occurrence of autoantibodies during treatment. Patients with pre-existing autoantibodies significantly less often developed irAEs during therapy than autoantibody-negative patients. New occurrence of the majority of autoantibodies during therapy was not significantly linked to irAE incidence. We only found a significant correlation between the presence of anti-thyroid peroxidase/anti-thyroglobulin during maintenance therapy with thyroid dysfunction development. While a significant association between pre-existing autoantibodies and disease control was not observed, we found a significant correlation between the occurrence of novel autoantibodies during therapy and a higher disease control rate for RCC patients. Moreover, patients with treatment-associated irAEs significantly more often achieved disease control.

CONCLUSIONS

Our findings revealed that neither the presence of autoantibodies at baseline nor the new occurrence of the majority of investigated autoantibodies during ICI therapy did predict irAE development in RCC patients. However, the appearance of novel autoantibodies and irAEs during therapy may represent markers for treatment efficacy.