Prognostic Impact of Immune-Related Adverse Events on Combination Immune Checkpoint/Tyrosine Kinase Inhibition for Metastatic Renal Cancer.

Immune checkpoint inhibitor (ICI) combinations and tyrosine kinase inhibitor (TKI) use are standard for metastatic renal cell carcinoma (mRCC), leading to improved outcomes. However, due to a lack of predictive biomarkers, the presence or absence of immune-related adverse events (irAE) is currently used as a predictive factor in clinical practice. To elucidate the impact of irAEs on efficacy, a cohort of patients with mRCC who received ICI-based combination therapy as initial treatment was analyzed. Patients were divided into two groups: those who received dual-ICI therapy (ICI-ICI, N = 55) or ICI and TKI therapy (ICI-TKI, N = 55). Subsequent to this initial categorization, each group was further subdivided based on the presence or absence of irAEs. In the ICI-ICI group, patients with irAEs exhibited significantly prolonged overall survival (OS) and progression-free survival [PFS; OS (median): not reached vs. 17.9 months, P = 0.03/PFS (median): 51.4 vs. 5.8 months, P SignificanceIn patients with mRCC who received ICI-ICI, the occurrence of irAEs was associated with improved survival outcomes, whereas no such association was observed in patients who received ICI-TKI. This suggests that irAEs may reflect the favorable immune response specific to ICI-ICI therapy, whereas differences in the tumor microenvironment, particularly involving neutrophils, in ICI-TKI patients may influence treatment response.