Reduced efficacy of nivolumab following prior immunotherapy in metastatic renal cell carcinoma: Implications for sequential immune checkpoint inhibition

Aim: To evaluate the effect of first-line interferon therapy on survival outcomes in patients treated with nivolumab for renal cell carcinoma (RCC). Methods: This retrospective study included 67 patients with mRCC who received nivolumab between March 2016 and September 2024 at our institution. Patients were stratified according to whether they had received interferon as first-line therapy. Survival outcomes following nivolumab were compared between the interferon and non-interferon groups. Results: Among the 67 patients, 47 (70.1%) were male and 20 (29.9%) were female. At diagnosis, 36 patients (53.8%) had metastatic disease. Patients previously treated with interferon had a median progression-free survival (mPFS) of 6.7 months with nivolumab, compared with 13.7 months among those without prior interferon (p = 0.049). Similarly, the median overall survival (mOS) was 7.2 months in the interferon group versus 23.0 months in the non-interferon group (p = 0.003). Conclusion: Prior interferon therapy appears to diminish the efficacy of subsequent nivolumab treatment in mRCC, suggesting potential limitations to sequential ICI strategies. These findings highlight the need for prospective studies to optimize the sequencing of immunotherapeutic agents in mRCC.