Experience of the nivolumab use in patients with metastatic renal cell carcinoma provided under the expanded access program in Russia. Subgroup analysis of the correlation between expression markers and the effectiveness of nivolumab therapy

Nivolumab was registered in Russia in December 2016 as a monotherapy for advanced renal cell carcinoma (RCC) and it remains a second-line treatment choice for patients with disease progression after the use of tyrosine kinase inhibitors. Even though immunotherapy has already proven to be an effective approach for the treatment of RCC, predictive biomarkers for the rational selection of patients remain unidentified. Seventy-five patients with metastatic renal cell carcinoma (mRCC) who received nivolumab in the 2nd and subsequent lines of therapy from 2015 to 2020 under the expanded access program were enrolled in this study. The objective response rate was 21,3%. Median progression-free survival (PFS) was 5,5 months. Median overall survival (OS) was not reached. To analyze molecular biomarkers correlated with the response to immunotherapeutic treatment, we performed whole-transcriptome RNA sequencing of 16 samples (FFPE) in 15 patients with the assessment of the expression level for individual genes (PDCD1, CD274, CD8A, CD8B, CD4) and gene signatures (Angio, Teff, Myeloid Inflammation). Disease control rates were not different for the subgroups of patients with high and low expression of any of the signatures examined, and further principal component analysis did not reveal clustering of patients with and without objective response. Further studies on a larger sample of patients will help confirm or deny the predictive role of biomarkers selected for analysis in a heterogeneous population of RCC patients.