Association of Cutaneous Immune-Related Adverse Events with Increased Survival in Patients Treated with Anti-Programmed Cell Death 1 and Anti-Programmed Cell Death Ligand 1 Therapy

Importance: Despite the efficacy of immune checkpoint inhibitors (ICIs), cutaneous immune-related adverse events (cirAEs) occur in 20% to 40% of all treated patients. To our knowledge, little is known about the predictive value of these cutaneous eruptions and their subtypes regarding cancer survival. Objective: To determine the association of developing cirAEs following treatment with anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) therapy with patient survival. Design, Setting, and Participants: This retrospective cohort study used data from the TriNetX Diamond Network, a database of health records and claims data from more than 200 million US and European patients, to conduct a population-level cohort analysis. The study included 7008 eligible patients who developed cirAEs after treatment with anti-PD-1 or anti-PD-L1 therapy for malignant neoplasms of digestive organs, bronchus or lung, melanoma of skin, and urinary tract who were identified through the TriNetX Diamond Network along with 7008 matched controls. Exposures: Development of cirAEs within 6 months following anti-PD-1 or anti-PD-L1 therapy. Main Outcomes and Measures: A 6-month analysis using a Cox proportional hazards model was performed to determine the association of cirAEs with overall survival after adjusting for demographic characteristics, cancer type, and cancer stage. Results: A total of 7008 patients (3036 women [43.3%]; mean [SD] age, 68.2 [11.2] years) were matched to 7008 (3044 women [43.4%]; mean [SD] age, 68.3 [11.1] years) controls. Pruritus (hazard ratio [HR], 0.695; 95% CI, 0.602-0.803; P <.001), drug eruption (HR, 0.755; 95% CI, 0.635-0.897; P =.001), xerosis (HR, 0.626; 95% CI, 0.469-0.834; P =.001), nonspecific rashes (HR, 0.704; 95% CI, 0.634-0.781; P <.001), and appearance of any cirAE (HR, 0.778; 95% CI, 0.726-0.834; P <.001) were significantly protective of mortality using a Benjamini-Hochberg correction with a significance level of.05. Additionally, psoriasis (HR, 0.703; 95% CI, 0.497-0.994; P =.045) and lichen planus/lichenoid dermatitis (HR, 0.511; 95% CI, 0.279-0.939; P =.03) were significant. Eczematous dermatitis (HR, 0.612; 95% CI, 0.314-1.195), vitiligo (HR, 0.534; 95% CI, 0.254-1.123), bullous pemphigoid (HR, 0.524; 95% CI, 0.140-1.956), and Grover disease (HR, 0.468; 95% CI, 0.115-1.898) were all associated with strong protective clinical effects. Conclusions and Relevance: The results of this cohort study suggest that the development of cirAEs is strongly associated with response to ICI therapy and patient survival..