Immune-checkpoint inhibitors (ICIs) have significantly improved outcomes in a variety of malignancies. Immune-related adverse events, however, are common and may lead to treatment discontinuation and adverse events. Immune-related cutaneous adverse events (ircAEs) are the most frequent and earliest to develop, but there is no evidence-based consensus regarding the management of these events. In this retrospective analysis, 285 patients with 427 ircAEs related to ICIs were studied to assess the efficacy of topical and systemic treatments prescribed by dermatologists. The most common ircAEs were pruritus (32%) and maculopapular rash (28%). Researchers found that ircAE phenotype was not associated with primary cancer diagnosis, but was associated with ICI class (p=0.007), in that maculopapular rash was predominant in patients who received combination therapy. Furthermore, dermatologic interventions such as topical corticosteroids, oral anti-pruritics, and systemic immunomodulators significantly reduced the severity of ircAEs (mean Common Terminology Criteria for Adverse Events grade 1.74 at diagnosis vs. 0.71 at follow-up, p=0.001). The largest improvement was observed in maculopapular rashes (mean grade reduction -1.40). Treatment patterns did not differ significantly between dermatologists (p=0.06). In all seven patients with corticosteroid-refractory ircAEs, targeted biologic immunomodulatory therapies improved symptoms. Several biomarkers were elevated in patients with ircAEs: serum interleukin-6 (IL-6) was elevated in 52% of patients, and mean immunoglobulin E serum levels were greater in higher-grade ircAEs. Additionally, grade 3 or higher ircAEs were associated with increased absolute eosinophils (OR 4.1, 95% CI 1.3 to 13.4) and IL-10 (OR 23.8, 95% CI 2.1 to 262.5). In summary, this study demonstrates that most patients with ircAEs were treated effectively with dermatologic interventions, and provides a basis for further controlled trials aimed at validating the safety and efficacy of these treatments in ircAEs and other immune-related adverse events. Finally, this study identified eosinophils, IL-6, IL-10, and immunoglobulin E as potential actionable therapeutic targets for immune-related skin toxicities.
Click to read the study in JCO
Image: PD
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