Clinical associations and classification of immune checkpoint inhibitors‐induced cutaneous toxicities: A multicentric study from the EADV‐Task Force of Dermatology for Cancer Patients

Background Cutaneous immune-related adverse events (irAEs) represent the most frequent toxicities induced by immune checkpoint inhibitors (ICI). Objectives To investigate clinical associations of cutaneous toxicities induced by different ICI therapies. Methods Multi-centric retrospective international cohort study of cancer patients, who developed cutaneous irAEs under ICI. Rates and basic characteristics analysis of all cutaneous toxicities and identification of any associations, using univariate and multivariate models were performed. Results 762 patients who developed 993 cutaneous toxicities were included. Forty different types of skin toxicities were identified. Psoriasis (175 patients, 23%) and pruritus (171 patients, 22.4%) were the most common toxicities followed by macular rash (161 patients, 21.1%) and eczematous-type reactions (150 patients, 19.7%). Multivariate analysis showed that among patients with macular rash, vitiligo, and multiple toxicities, patients with melanoma received ICI more frequently than for NSCLC. Moreover, anti-CTLA4 was less frequent than anti-PD1 treatment in patients with macular rash (OR 0.11, 95%CI 0.01 - 0.76) and vitiligo (OR=0.07, 95%CI 0.006 – 0.82). The same significant association was shown in patients with psoriasis (OR 0.08, 95%CI 0.02- 0.31) , lichenoid (OR 0.15, 95%CI 0.03 – 0.77) and eczematous reactions (OR 0.24, 95%CI 0.07 – 0.78), all compared to pruritic rash, who received combination of ICI plus chemotherapy and compared to ICI monotherapy. Conclusions Our study showed that skin-oriented toxicities do not share a unanimous 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.