Association of K1505Ac IHC signal loss and response to immunotherapy in patients with metastatic cutaneous melanoma.

Abstract

e22049 Background: Immune checkpoint inhibitors (ICI) have become a mainstay of treatment for patients with metastatic cutaneous melanoma. Currently, there are no reliable biomarkers to predict which patients will benefit from ICI therapy. K1505Ac immunohistochemistry (IHC) signal loss is equivalent to loss of functional PBRM1 protein, which has previously been shown to predict response to ICI therapy in metastatic renal cell carcinoma. We hypothesized that loss of K1505Ac IHC expression in patients’ tumors may predict benefit to ICI therapy. Methods: An exploratory study was conducted in patients with metastatic cutaneous melanoma (n = 25) who were treated with ICI therapy at Thomas Jefferson University. Retrospective chart review was performed to determine best clinical response using RECIST 1.1 criteria. Tumor samples from these patients were tested for loss of K1505Ac IHC signals to determine the correlation to best clinical response to ICI therapy. The pathologist was blinded to clinical responses during IHC analysis. Results: The chart below demonstrates the percentage of patients with K1505Ac IHC signal loss ≥ 40% and their correlating best clinical response to ICI therapy. Four of five patients (80%) with complete or partial response displayed K1505Ac IHC signal loss ≥ 40%. Fifteen of twenty patients (75%) with stable disease or progression of disease displayed K1505Ac IHC signal loss < 40%. Conclusions: Loss of K1505Ac IHC signal was associated with better clinical response to ICI therapy for patients with metastatic cutaneous melanoma. These findings suggest that K1505Ac IHC signal loss may serve as a biomarker to help determine which patients will benefit from ICI therapy. A larger cohort of patients is currently under investigation to better evaluate this association. [Table: see text]