Cutaneous immune-related adverse events are associated with longer overall survival in advanced cancer patients on immune checkpoint inhibitors: A multi-institutional cohort study

Abstract

Background: Cutaneous immune-related adverse events (cirAEs) occur in up to 40% of immune checkpoint inhibitor (ICI) recipients. However, the association of cirAEs with survival remains unclear.

Objective: To investigate the association of cirAEs with survival among ICI recipients.

Methods: ICI recipients were identified from the Mass General Brigham healthcare system and Dana-Farber Cancer Institute. Patient charts were reviewed for cirAE development within 2 years after ICI initiation. Multivariate time-varying Cox proportional hazards models, adjusted for age, sex, race/ethnicity, Charlson Comorbidity Index, ICI type, cancer type, and year of ICI initiation were utilized to investigate the impact of cirAE development on overall survival.

Results: Of the 3731 ICI recipients, 18.1% developed a cirAE. Six-month landmark analysis and time-varying Cox proportional hazards models demonstrated that patients who developed cirAEs were associated with decreased mortality (hazardratio [HR] = 0.87, P = .027), particularly in patients with melanoma (HR = 0.67, P = .003). Among individual morphologies, lichenoid eruption (HR = 0.51, P < .001), psoriasiform eruption (HR = 0.52, P = .005), vitiligo (HR = 0.29, P = .007), isolated pruritus without visible manifestation of rash (HR = 0.71, P = .007), acneiform eruption (HR = 0.34, P = .025), and non-specific rash (HR = 0.68, P < .001) were significantly associated with better survival after multiple comparisons adjustment.

Limitations: Retrospective design; single geography.

Conclusion: CirAE development is associated with improved survival among ICI recipients, especially patients with melanoma.

Keywords: cutaneous adverse reactions; immune checkpoint inhibitor; immune-related adverse events; immunotherapy; melanoma; mortality; oncology; skin toxicity.