Background
Adjuvant immunotherapy is currently the standard of care for patients with resected renal cell carcinoma (RCC) at increased risk of recurrence, but there are no biomarkers available to guide treatment. Kidney injury molecule-1 (KIM-1) has previously been described as a potential circulating biomarker in RCC.
Patients and methods
Biomarkers and outcomes among patients who participated in a randomized phase III trial of adjuvant atezolizumab versus placebo in resected RCC (IMmotion010) were evaluated. This trial did not meet its primary endpoint of disease-free survival (DFS) in the intention-to-treat population. An affinity-based proximity extension proteomics assay was used to compare levels of circulating proteins among baseline (post-nephrectomy) serum samples and samples taken at the time of recurrence.
Results
Serum KIM-1 was the most significantly enriched protein at recurrence versus baseline. Patients with serum KIM-1high at baseline had worse DFS [hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.35-2.09], but also had improved DFS when treated with adjuvant atezolizumab versus placebo (HR 0.72, 95% CI 0.52-0.99). An increase in KIM-1 during follow-up was associated with worse DFS compared with patients with no increase in KIM-1. Within the KIM-1high subgroup, longer DFS following atezolizumab treatment was associated with increased baseline expression of T-effector and Th1 signatures, while shorter DFS was associated with increased baseline expression of matrix remodeling genes and protumor cytokines.
Conclusion
These analyses suggest that elevated post-nephrectomy plasma KIM-1 level and kinetics are prognostic, supporting the hypothesis that KIM-1 is a biomarker for minimal residual disease in RCC. As KIM-1high patients are also enriched for benefit from adjuvant immunotherapy, biomarker-driven adjuvant therapy should be evaluated as a potential new paradigm in RCC.
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