Eosinophil Dynamics May Help Differentiate Immune-Related From TKI-Related Adverse Events During IO-TKI Therapy for...

Combination therapy with immune checkpoint inhibitors and tyrosine kinase inhibitors (IO-TKI) is a key treatment option for metastatic renal cell carcinoma (mRCC), but distinguishing immune-related adverse events (irAEs) from TKI-related adverse events (TKI-AEs) is challenging because of overlapping clinical features. We aimed to evaluate whether eosinophil counts can help differentiate between them.

In this retrospective multicenter study, 123 patients with mRCC treated with IO-TKI therapy were analyzed. Patients were classified into an irAE group (n = 64) and a TKI-AE group (n = 59). Changes in eosinophil counts from baseline to the start of the second treatment cycle were compared. Receiver operating characteristic (ROC) and logistic regression analyses were performed to assess associations with irAE occurrence.

Baseline eosinophil counts did not differ between groups. Eosinophil counts at the start of the second treatment cycle were higher in the irAE group than those in the TKI-AE group (269.6 vs. 189.6 eosinophils/μL; p < 0.05). No significant differences were observed in other blood parameters, including neutrophil, lymphocyte, monocyte, and platelet counts, the neutrophil-to-lymphocyte ratio, or the platelet-to-lymphocyte ratio. Although the overall discriminatory performance was modest (area under the ROC curve = 0.57, sensitivity = 0.30, specificity = 0.94), eosinophil counts ≥ 380/μL were associated with irAEs in both univariate (odds ratio = 7.21) and multivariable (odds ratio = 8.39; p < 0.05) analyses.

Early increases in eosinophil counts were associated with irAEs and may help distinguish irAEs from TKI-AEs during IO-TKI therapy. Given their high specificity but limited sensitivity, eosinophil counts may have utility as an adjunctive rather than stand-alone marker, and prospective validation is warranted.