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Importance Cutaneous immune-related adverse events (cirAEs) are some of the earliest toxic reactions to emerge following immune-checkpoint inhibitor (ICI) initiation. As an early indicator of robust inflammatory response, cirAEs may be associated with patterns of immune-mediated toxic effects, but associations between these events and noncutaneous immune-related adverse events (irAEs) remain underexplored. Objectives To characterize patterns of cirAEs and irAEs across care settings and examine associations between the features of first cirAE, overall irAE risk, and risk of specific irAE subtypes. Design, Setting, and Participants A retrospective cohort study was conducted at a single academic medical center. The cohort included 358 patients with cancer who initiated anti–programmed death 1/ligand 1 and/or anticytotoxic-T-lymphocyte-4 ICI therapy between January 1, 2016, and March 8, 2019, and developed 1 or more cirAEs, identified usingInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and confirmed via manual medical record review. All relevant information documented before March 31, 2020, was included. Exposures Anti–programmed death 1/ligand 1 and/or anticytotoxic-T-lymphocyte-4 therapy. Main Outcomes and Measures Associations between specific cirAE morphologic classes and patterns of irAEs (occurrence, timeline, organ class, and specific toxic effects). Given the potential that shared underlying factors are associated with the risk of both noncutaneous and cutaneous toxic effects, the presence of observed positive associations between certain cirAE and irAE subtypes was hypothesized. Results Of the 358 patients, 213 were men (59.5%); median age was 65 years (interquartile range, 55-73 years). Nearly half of the patients (177 [49.4%]) with cirAE also developed a noncutaneous irAE. Most patients (128 [72.3%]) experienced their first cirAE before developing any irAE. Several cirAE morphologic classes were found to be associated with overall, organ-based, and specific irAEs. More specifically, mucositis was found to be associated with overall irAE risk (odds ratio [OR], 5.28; 95% CI, 1.11-24.26;P = .04), gastrointestinal irAEs (OR, 5.70; 95% CI, 1.11-29.40;P = .04), and the specific diagnosis of gastroenterocolitis (OR, 6.80; 95% CI, 1.24-37.39;P = .03). In addition, psoriasis was associated with an increased risk of endocrine irAEs (OR, 4.54; 95% CI, 1.21-17.04;P = .03). Conclusions and Relevance In this cohort study, these findings underscore the risk of multisystem toxic effects in patients experiencing cirAEs and highlight potential opportunities for dermatologists in the management of noncutaneous toxic effects.

BACKGROUND Cutaneous immune-related adverse events (cirAEs) are a common side-effect of immune checkpoint inhibitors (ICIs). However, prior work examining these toxicities in detail has considered only the fraction of events evaluated by dermatologists. Associations between dermatology referral, cirAE treatment and survival outcomes remain underexplored across care settings. OBJECTIVES To comprehensively categorize cirAE patterns among all patients treated with immunotherapy at our institution, and to evaluate: (i) the effect of dermatology referral on cirAE treatment and (ii) the impact of cirAE treatment on survival. METHODS This was a retrospective cohort analysis of patients with cancer who initiated ICI therapy between 1 January 2016 and 8 March 2019 and developed one or more cirAEs, as screened for using International Classification of Diseases 10th revision codes and confirmed via manual chart review (n = 358). All relevant information documented prior to 31 March 2020 was included. RESULTS CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred (odds ratio 6·08, P

Immune checkpoint inhibitors (ICIs) have improved survival for multiple malignancies in adults and children.1,2 However, their benefits are tempered by a range of serious immune-related adverse events (irAEs). 1,2 Among these, cutaneous irAEs (cirAEs) represent one of the most common subtypes, impacting approximately one-third of adult patients receiving ICIs.1,3 The patterns and significance of cirAEs in children remain unclear, largely because these reactions have not been evaluated in detail.

e14523 Background: Cutaneous immune-related adverse events (cirAE) may disrupt immune-checkpoint inhibitor (ICI) therapy. Current guidelines recommend systemic corticosteroids (SCS) for moderate to severe cirAE, but SCS-associated complications and their impact on survival remain poorly understood. We therefore investigated the impact of SCS exposures on infectious complications and survival outcomes among patients with cirAE. Methods: We retrospectively reviewed the medical records of patients who initiated anti-programmed death-1/ligand-1 (PD-1/PDL-1) and/or anti-cytotoxic-T-lymphocyte-4 (CTLA-4) ICI therapy between 1/1/16-3/8/19 with confirmed cirAE, obtaining oncologic history, clinical features, SCS exposures, infection rates, and survival outcomes. SCS exposures were categorized by indication (cirAE, other immune-related adverse event, other medical reason) and dosage in prednisone equivalents (low, ≤7.5mg/day for ≥2 months; moderate, > 7.5mg/day for ≥2 months; high, ≥1mg/kg/day for ≥1 week). Infection rates were compared among patients treated with SCS for initial cirAE and those with no SCS exposures for any indication. Cox proportional hazards (CPH) models adjusted for age, sex, and covariates with P