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.