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

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 PARTICIPANTSThis 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 MEASURESA 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.

Safety of Immune Checkpoint Inhibitor Resumption after Interruption for Immune-Related Adverse Events, a Narrative Review

“…A growing body of evidence suggests that irAE occurrence is predictive of anti-PD(L)-1) response with a marked improvement in progression-free survival, OS and overall response rate in patients with irAE compared to those without [ 72 ]. Moreover, some specific irAEs are associated with enhanced survival, cutaneous irAEs being one of the best documented examples [ 73 , 74 , 75 , 76 , 77 ]. However, to date, whether or not specific irAE-related factors (severity, timing of onset, therapeutic intervention, irAE recurrence) are associated with increased OS remains unknown and questions the need for ICI resumption after ICI discontinuation due to irAE.…”

Networks of CD8+ T Cell Response Activation in Melanoma and Vitiligo

“…Vitiligo and antitumor responses in melanoma reportedly depend on CD8 + T cells that recognize identical antigens, so-called melanocyte/melanoma-shared antigens (MSA), including Melan-A, tyrosinase, and premelanosome (PMEL), and can reduce melanoma mass and prevent tumor recurrence (2). Indeed, vitiligo induced by immunotherapy is strongly associated with response to ICI therapy and patient survival (3). These results suggest that MSA-specific CD8 + T cell responses promote vitiligo progression and can suppress melanoma progression and vice versa.…”

Contribution of the Skin–Gut Axis to Immune-Related Adverse Events with Multi-System Involvement

“…Various organ systems can be affected by irAEs, though the skin, gastrointestinal, endocrine, and pulmonary systems are affected most often. It is unclear why some patients are more affected by irAEs than others, although some evidence suggests that irAEs may be associated with increased ICB efficacy and patient survival [ 5 , 6 , 7 ].…”