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. 2022 Feb 1;158(2):189-193.
doi: 10.1001/jamadermatol.2021.5476.

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

Kimberly Tang  1 , Jayhyun Seo  1 , Bruce C Tiu  1   2 , Thomas K Le  3 , Vartan Pahalyants  1   2 , Neel S Raval  1   2   4 , Pearl O Ugwu-Dike  1 , Leyre Zubiri  5 , Vivek Naranbhai  5 , Mary Carrington  6   7   8 , Alexander Gusev  9 , Kerry L Reynolds  5 , Nicole R LeBoeuf  10 , Maryam M Asgari  1   2   11 , Shawn G Kwatra  3 , Yevgeniy R Semenov  1   2
Affiliations

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

Kimberly Tang et al. JAMA Dermatol. .

Abstract

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Zubiri reported personal fees from Merck outside the submitted work. Dr LeBoeuf reported personal fees from Bayer, Synox, Seattle Genetics, Sanofi, and Silverback Therapeutics outside the submitted work. Dr Asgari reported grants from Pfizer outside the submitted work. Dr Semenov reported personal fees from Castle Biosciences and Incyte Corporation outside of the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Study Flow Diagram
cirAE indicates cutaneous immune-related adverse events; PD-1, programmed cell death 1; PD-L1, programmed cell death ligand 1.
See this image and copyright information in PMC

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