학술논문
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.
Document Type
Academic Journal
Author
Tang K; Massachusetts General Hospital, Department of Dermatology, Boston.; Seo J; Massachusetts General Hospital, Department of Dermatology, Boston.; Tiu BC; Massachusetts General Hospital, Department of Dermatology, Boston.; Harvard Medical School, Department of Dermatology, Boston, Massachusetts.; Le TK; Johns Hopkins University, Department of Dermatology, Baltimore, Maryland.; Pahalyants V; Massachusetts General Hospital, Department of Dermatology, Boston.; Harvard Medical School, Department of Dermatology, Boston, Massachusetts.; Raval NS; Massachusetts General Hospital, Department of Dermatology, Boston.; Harvard Medical School, Department of Dermatology, Boston, Massachusetts.; Washington University School of Medicine, St Louis, Missouri.; Ugwu-Dike PO; Massachusetts General Hospital, Department of Dermatology, Boston.; Zubiri L; Massachusetts General Hospital, Department of Medicine, Division of Oncology, Boston.; Naranbhai V; Massachusetts General Hospital, Department of Medicine, Division of Oncology, Boston.; Carrington M; Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, Maryland.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge.; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.; Gusev A; Dana Farber Cancer Institute, Department of Medicine, Boston, Massachusetts.; Reynolds KL; Massachusetts General Hospital, Department of Medicine, Division of Oncology, Boston.; LeBoeuf NR; Dana Farber Cancer Institute, Department of Dermatology, Boston, Massachusetts.; Asgari MM; Massachusetts General Hospital, Department of Dermatology, Boston.; Harvard Medical School, Department of Dermatology, Boston, Massachusetts.; Department of Population Medicine, Harvard Medical School, Boston, Massachusetts.; Kwatra SG; Johns Hopkins University, Department of Dermatology, Baltimore, Maryland.; Semenov YR; Massachusetts General Hospital, Department of Dermatology, Boston.; Harvard Medical School, Department of Dermatology, Boston, Massachusetts.
Source
Publisher: American Medical Association Country of Publication: United States NLM ID: 101589530 Publication Model: Print Cited Medium: Internet ISSN: 2168-6084 (Electronic) Linking ISSN: 21686068 NLM ISO Abbreviation: JAMA Dermatol Subsets: MEDLINE
Subject
Language
English
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.
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.