Skin Abnormalities at Checkpoint Inhibitor Therapy Initiation Are Associated With Skin Rash Development in Oncology Patients.

Abstract

Immune-related cutaneous adverse events (ircAEs) complicate management in many cancer patients receiving checkpoint inhibitor (CPI) immunotherapy. A new approach to early prognosis and ircAE treatment monitoring is needed in order to improve patient adherence to CPI immunotherapy. Skin tape strips (STS) and plasma were collected prospectively from 22 oncology patients prior to starting CPI and after 6 weeks of CPI therapy. Patients were then followed for ircAE development for 6 months. Ten patients subsequently developed ircAEs. STS were analyzed for cytokines and lipids, while plasma was analyzed for cytokines. A significant increase in stratum corneum (SC) ceramides with short chain fatty acids was observed in patients who developed ircAEs (p < 0.05 compared to non-ircAE groups). This lipid abnormality was already present in the skin of future ircAE patients before starting CPI immunotherapy, and was further dysregulated on CPI therapy. Following CPI initiation, significant increases in skin (but not plasma) IL-8, IL-18, and IP-10 (CXCL10), IL-12, IFNa, MDC (CCL22), and TARC (CCL17) production were observed in patients who subsequently developed ircAEs (p < 0.05 compared to non-ircAE groups). STS analysis of patients developing ircAEs demonstrated SC lipid abnormalities prior to CPI treatment. When studied after 6 weeks of CPI therapy, these SC barrier lipid abnormalities were worsened. In addition, significant increases in proinflammatory cytokine levels were identified in the skin, but not in plasma. These findings point to mechanisms of ircAE development and may allow early identification of patients at risk of developing ircAEs for close monitoring and future prevention of treatment-limiting ircAEs.