Objectives: The management of metastatic renal cell carcinoma (RCC) in the third-line setting presents significant challenges due to limited data on treatment options beyond first-line and second-line therapies. Immunotherapy rechallenge with immune checkpoint inhibitors has emerged as a potential strategy for selected patients who previously responded to initial treatment but experienced disease progression. This study aimed to evaluate the effectiveness of nivolumab in patients previously treated with interferon alpha and anti-vascular endothelial growth factor therapies. Methods: A total of 54 adult patients with metastatic RCC were included. Demographic data, International Metastatic RCC Database Consortium (IMDC) risk scores, pre-treatment laboratory findings, and previous treatment lines were reviewed retrospectively. Overall and progression-free survival (OS and PFS) outcomes were analyzed by statistical tests. Results: The median OS and PFS were 25.3 (95% CI: 22.3-28.3) and 9.7 (95% CI: 4.8-14.6) months, respectively. No significant relationships were found between OS and sex (p=0.585), age (< vs. ?65 years, p=0.98), IMDC risk groups (p=0.39), second-line treatment (pazopanib vs. sunitinib, p=0.425) or nivolumab line (III vs. IV, p=0.249). PFS was consistent with OS in this sense. Conclusion: The median PFS of 9.7 months surpassed previous data on immunotherapy rechallenge, suggesting a potential benefit of interferon alfa in enhancing immunotherapy response. Keywords: Immunotherapy, metastatic renal cell carcinoma, interferon alpha, nivolumab.
Corresponding Author: Elvina Almuradova