Work

Circulating kidney injury molecule-1 (KIM-1) and association with outcome to adjuvant immunotherapy in renal cell carcinoma

Year: 2025

Type: article

Abstract: 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 renal cell carcinoma. 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 DFS endpoint 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 time of recurrence. Results Serum KIM-1 was the most significantly enriched protein at recurrence versus baseline. Patients with serum KIM-1 high at baseline had worse disease-free survival (DFS) (hazard ratio 1.68, 95% CI 1.35-2.09), but also had improved DFS when treated with adjuvant atezolizumab versus placebo (hazard ratio 0.72, 95% CI 0.52-0.99). An increase in KIM-1 during follow-up was associated with worse DFS compared to patients with no increase in KIM-1. Within the KIM-1 high 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-1 high patients are also enriched for benefit from adjuvant immunotherapy, biomarker driven adjuvant therapy should be evaluated as a potential new paradigm in RCC.

Source: Annals of Oncology

DOI: 10.1016/j.annonc.2025.08.007