Clinical associations and classification of immune checkpoint inhibitor-induced cutaneous toxicities: a multicentre study from the European Academy of Dermatology and Venereology Task Force of Dermatology for Cancer Patients

Background Cutaneous immune-related adverse events (irAEs) represent the most frequent toxicities induced by immune checkpoint inhibitors (ICIs). Objectives To investigate clinical associations of cutaneous toxicities induced by different ICI therapies. Methods This was a multicentre retrospective international cohort study of patients with cancer who developed cutaneous irAEs under ICI therapy. Analysis was performed of the rates and basic characteristics of all cutaneous toxicities, and identification of any associations was performed using univariate and multivariate models. Results In total, 762 patients were included, who developed 993 cutaneous toxicities. Forty different types of skin toxicities were identified. Psoriasis (175 patients, 23 center dot 0%) and pruritus (171 patients, 22 center dot 4%) were the most common toxicities, followed by macular rash (161 patients, 21 center dot 1%) and eczematous-type reactions (150 patients, 19 center dot 7%). Multivariate analysis showed that among patients with macular rash, vitiligo or multiple toxicities, patients received ICIs more frequently for melanoma than for NSCLC. Moreover, anti-CTLA4 was less frequent than anti-programmed death 1 treatment in patients with macular rash [odds ratio (OR) 0 center dot 11, 95% confidence interval (CI) 0 center dot 01-0 center dot 76] and vitiligo (OR 0 center dot 07, 95% CI 0 center dot 006-0 center dot 78). A significant association was also seen in patients treated with a combination of ICI and chemotherapy vs. ICI monotherapy. They less frequently developed psoriasis (OR 0 center dot 08, 95% CI 0 center dot 02-0 center dot 31), lichenoid reactions (OR 0 center dot 15, 95% CI 0 center dot 03-0 center dot 77) and eczematous reactions (OR 0 center dot 24, 95% CI 0 center dot 07-0 center dot 78), all compared with pruritic rash. Conclusions Our study showed that skin-oriented toxicities do not share a single pattern and are related to several factors, including the specific agent administered and the underlying malignancy treated. Follow-up plans should be individualized in order to minimize the risk for severe reactions that could compromise optimum therapeutic outcome. What is already known about this topic? Patients with cancer treated with different immune checkpoint inhibitors (ICIs) carry an increased risk of developing various types of skin toxicities. What are the clinical implications of this work? In this multicentre cohort study we showed that ICI-related skin toxicities do not share a single pattern and may depend on several factors, including the specific agent administered and the underlying malignancy. Among patients with macular rash, vitiligo or multiple skin toxicities, patients received ICIs more frequently for melanoma than for non-small cell lung cancer. The combination of ICI and chemotherapy compared with ICI monotherapy occurred to a lesser extent in patients with psoriatic rash lichenoid and eczematous reactions, compared with patients with pruritus. Clinical awareness and specialized dermatological consultation should be advocated.

Automated summary

The study demonstrates that ICI-related skin toxicities do not share a single pattern and may depend on several factors, including the specific drug administered and the underlying malignancy. Patients with macular rash, vitiligo, or multiple skin toxicities were more frequently treated with ICIs for melanoma rather than non-small cell lung cancer. The combination of ICI and chemotherapy compared to ICI monotherapy was associated with a lower incidence of psoriatic rash, lichenoid, and eczematous reactions in patients, compared to those with pruritic rash.