Treatment Outcomes of Immune-Related Cutaneous Adverse Events

Abstract

PURPOSE The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled cohort of patients referred to oncodermatology clinics. METHODS A retrospective analysis of patients with ircAEs evaluated by dermatologists from January 1, 2014, to December 31, 2017, at three tertiary care hospitals and cancer centers were identified through electronic medical records. Clinicopathologic characteristics, dermatologic therapy outcome, and laboratory data were analyzed. RESULTS A total of 285 patients (median age, 65 years [range, 17 to 89 years]) with 427 ircAEs were included: pruritus (n = 138; 32%), maculopapular rash (n = 120; 28%), psoriasiform rash (n = 22; 5%), and others (n = 147; 34%). Immune checkpoint inhibitor class was associated with ircAE phenotype ( P = .007), where maculopapular rash was predominant in patients who received combination therapy. Severity of ircAEs was significantly reduced (mean Common Terminology Criteria for Adverse Events grade: 1.74 v 0.71; P < .001) with dermatologic interventions, including topical corticosteroids, oral antipruritics, and systemic immunomodulators. A total of 88 ircAEs (20%) were managed with systemic immunomodulators. Of these, 22 (25%) of 88 persisted or worsened. In seven patients with corticosteroid-refractory ircAEs, improvement resulted from targeted biologic immunomodulatory therapies that included rituximab and dupilumab. Serum interleukin-6 (IL-6) was elevated in 34 (52%) of 65 patients; grade 3 or greater ircAEs were associated with increased absolute eosinophils (odds ratio, 4.1; 95% CI, 1.3 to 13.4) and IL-10 (odds ratio, 23.8; 95% CI, 2.1 to 262.5); mean immunoglobulin E serum levels were greater in higher-grade ircAEs: 1,093 kU/L (grade 3), 245 kU/L (grade 2), and 112 kU/L (grade 1; P = .043). CONCLUSION Most ircAEs responded to symptom- and phenotype-directed dermatologic therapies, whereas biologic therapies were effective in patients with corticosteroid-refractory disease. Increased eosinophils, IL-6, IL-10, and immunoglobulin E were associated with ircAEs, and they may represent actionable therapeutic targets for immune-related skin toxicities.

Discordance between recommended and delivered therapies for immunotherapy‐associated cutaneous toxicities in pediatric populations

“…In this study, we evaluated discordance between recommended and delivered cirAE therapies. We found that cirAEs were common in children, mirroring rates previously reported in adults 5 . cirAE subtypes for which treatment guidelines were available were often untreated or undertreated despite their prevalence.…”

“…We retrospectively reviewed the records of patients aged 0‐21 years who received ICIs at Massachusetts General and Boston Children's Hospitals between 2010 and 2019, identifying individuals who developed cirAEs. cirAEs were defined as eruptions emerging after ICI initiation, consistent with established morphologic categories and attributed to the ICI by the treating clinician 5,6 . Additional inclusion criteria were involvement of >1% body surface area and duration >1 day.…”

Moderate-to-severe eosinophilia induced by treatment with immune checkpoint inhibitors: 37 cases from a national reference center for hypereosinophilic syndromes and the French pharmacovigilance database

“…Increased AEC, serum IL-6, Il-10 and IgE levels were associated with corticosteroid-refractory adverse events and with grade 3 or greater cutaneous AEs, but the direct accountability of eosinophils was not assessed in these exceptional cases. 24 Even if some severe cutaneous AEs like drug reaction with eosinophilia and systemic symptoms (DRESS) require high-dose corticosteroids, 25,26 multiple recent reports of Eo-irAEs like eosinophilic fasciitis [27][28][29][30] or eosinophilic granulomatosis with polyangiitis 31 suggest that topical or low-dose oral corticosteroids, with or without CSsparing treatments, can give excellent results. Taking account these data, and given that in our work (i) Eo-ir and Eo-irAEs accounted for half of all ICI discontinuations and (ii) no deaths were directly attributable to eosinophil-organ damage, we suggest that the initiation of corticosteroids and the maintenance of the ICI might be an effective therapeutic strategy in patients with moderate-to-severe eosinophilia and whose cancer is under control.…”

Non-dermatological Challenges of Chronic Itch

“…Along with the expansive development and use of targeted tumour therapies, numerous reports have emerged about therapy-associated chronic pruritus (48)(49)(50)(51)(52). The neurokinin-1-antagonist aprepitant seems to have antipruritic potential in such cases (53).…”