medRxiv : the preprint server for health sciences · 2023
Cutaneous immune-related adverse events are associated with longer overall survival in advanced cancer patients on immune checkpoint inhibitors: a multi-institutional cohort study.
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Zhang Shijia, Tang Kimberly, Wan Guihong, Nguyen Nga, Lu Chenyue, Ugwu-Dike Pearl, Raval Neel, Seo Jayhyun, Alexander Nora A, Jairath Ruple, Phillipps Jordan, Leung Bonnie W, Roster Kathleen, Chen Wenxin, Zubiri Leyre, Boland Genevieve, Chen Steven T, Tsao Hensin, Demehri Shadmehr, LeBoeuf Nicole R, Reynolds Kerry L, Yu Kun-Hsing, Gusev Alexander, Kwatra Shawn G, Semenov Yevgeniy R
Аннотация
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 (MGB) and Dana-Farber Cancer Institute (DFCI). 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 3,731 ICI recipients, 18.1% developed a cirAE. 6-month landmark analysis and time-varying Cox proportional hazards models demonstrated that patients who developed cirAEs were associated with decreased mortality (HR=0.87,p=0.027), particularly in melanoma patients (HR=0.67,p=0.003). Among individual morphologies, lichenoid eruption (HR=0.51,p<0.001), psoriasiform eruption (HR=0.52,p=0.005), vitiligo (HR=0.29,p=0.007), isolated pruritus without visible manifestation of rash (HR=0.71,p=0.007), acneiform eruption (HR =0.34,p=0.025), and non-specific rash (HR=0.68, p<0.001) 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 melanoma patients.
CAPSULE SUMMARY: Patients on immune checkpoint inhibitors (ICIs) who developed cutaneous immune-related adverse events (cirAEs) had favorable outcomes. This was especially notable for melanoma patients who had cirAEs, both those with vitiligo and other morphologies.Development of cirAEs in ICI-treated patients can be used to prognosticate survival and guide treatment decisions.
OBJECTIVE: To investigate the association of cirAEs with survival among ICI recipients.
METHODS: ICI recipients were identified from the Mass General Brigham healthcare system (MGB) and Dana-Farber Cancer Institute (DFCI). 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 3,731 ICI recipients, 18.1% developed a cirAE. 6-month landmark analysis and time-varying Cox proportional hazards models demonstrated that patients who developed cirAEs were associated with decreased mortality (HR=0.87,p=0.027), particularly in melanoma patients (HR=0.67,p=0.003). Among individual morphologies, lichenoid eruption (HR=0.51,p<0.001), psoriasiform eruption (HR=0.52,p=0.005), vitiligo (HR=0.29,p=0.007), isolated pruritus without visible manifestation of rash (HR=0.71,p=0.007), acneiform eruption (HR =0.34,p=0.025), and non-specific rash (HR=0.68, p<0.001) 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 melanoma patients.
CAPSULE SUMMARY: Patients on immune checkpoint inhibitors (ICIs) who developed cutaneous immune-related adverse events (cirAEs) had favorable outcomes. This was especially notable for melanoma patients who had cirAEs, both those with vitiligo and other morphologies.Development of cirAEs in ICI-treated patients can be used to prognosticate survival and guide treatment decisions.