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Brief Report
January 12, 2022

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

Author Affiliations
  • 1Massachusetts General Hospital, Department of Dermatology, Boston
  • 2Harvard Medical School, Department of Dermatology, Boston, Massachusetts
  • 3Johns Hopkins University, Department of Dermatology, Baltimore, Maryland
  • 4Washington University School of Medicine, St Louis, Missouri
  • 5Massachusetts General Hospital, Department of Medicine, Division of Oncology, Boston
  • 6Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, Maryland
  • 7Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge
  • 8Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
  • 9Dana Farber Cancer Institute, Department of Medicine, Boston, Massachusetts
  • 10Dana Farber Cancer Institute, Department of Dermatology, Boston, Massachusetts
  • 11Department of Population Medicine, Harvard Medical School, Boston, Massachusetts
JAMA Dermatol. 2022;158(2):189-193. doi:10.1001/jamadermatol.2021.5476
Key Points

Question  What is the association of cutaneous immune-related adverse events (cirAEs) with mortality in treatment with immune checkpoint inhibitor (ICI) therapy for patients with cancer?

Findings  In this retrospective cohort study of 7008 patients with cancer who developed cirAEs after treatment with anti–programmed cell death 1 or anti–programmed cell death ligand 1 therapy and 7008 matched controls, a 6-month analysis suggested that the development of pruritus, drug eruption, xerosis, nonspecific rashes, and any cirAE as a group was significantly protective of mortality.

Meaning  The study results suggest that cirAE development after ICI treatment initiation is strongly associated with response to ICI therapy and patient survival.


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.

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