Potential biomarkers for nivolumab therapy of metastatic renal cell carcinoma

Background. Therapy with immune checkpoint inhibitors (antibodies against PD-1) has become a standard of treatment of patients with metastatic renal cell carcinoma (mRCC) resistant to tyrosine kinase inhibitors. Objective: to identify reliable immunological markers predicting mRCC sensitivity to nivolumab therapy to increase its effectiveness and facilitate its more rational application.

Materials and methods. The article presents an analysis of treatment of 23 patients with mRCC who received nivolumab under the expanded access program. Objective response rate in this group was 21.7 %. Median progression-free survival was 4 months (95 % confidence interval was 1.37–10.04). Median overall survival wasn’t reached for median follow-up duration of 10 months (3–14 months); grade III–IV complications were observed in 13 % of cases.

Results. During nivolumab therapy, factors positively affecting progrerssion-free survival were presence of clinical effect, favorable prognosis per the Memorial Sloan Kettering Cancer Center criteria, development of hypothyroidism, baseline serum levels of interleukin-17А and sPD-1 above the threshold values. Baseline increased serum concentration of TGF-β1 compared to the threshold level (20 ng/ml) was a negative prognostic factor for nivolumab immunotherapy. The number of previous therapy lines, PD-L1 and FOXP3 expression on tumor-infiltrating lymphocytes didn’t significantly affect progression-free survival. Effectiveness and toxicity profile of nivolumab in this series of observations conformed to the results of the phase III clinical trial. The drug was characterized by high tolerability.

Conclusion. The study results demonstrated lower toxicity and high tolerability of nivolumab compared to previously registered targeted drugs. Low rate of adverse events allows to study nivolumab in combined or subsequent/alternating modes of treatment with other immune checkpoint inhibitors and targeted drugs.

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