Risk factors for cutaneous immune-related adverse events: a systematic scoping review

Objective: To comprehensively summarize risk factors and explore potential mechanisms associated with cutaneous immune-related adverse events (cirAEs) in cancer patients treated with immune checkpoint inhibitors (ICIs). Method: Conducted in accordance with the PRISMA-ScR guidelines, this review included studies published in English and Chinese that investigated cirAEs risk factors in cancer patients receiving ICIs. A scoping review with systematic search criteria was conducted using PubMed, Embase, Cochrane, Web of Science, ProQuest, CINAHL, CNKI, Wanfang Data, VIP, and SinoMed from database inception to December to December 31, 2023. Results: 4905 studies were identified and 50 studies were included in this review, encompassing 198,514 participants. Among these, 12.5% experienced at least one cirAEs, with maculopapular rash, pruritus, and unspecified rash being the most common subtypes. A total of 68 distinct risk factors were identified from these studies, categorized into three primary risk domains: demographic factors, clinical characteristics, and biomarkers, including age, gender, BMI, smoking history, specific treatment regimens (e.g., camrelizumab), tumor type (e.g., melanoma), eosinophil count, and cytokine levels, among others. The odds ratios (OR) for reported risk factors demonstrated significant associations with specific cirAEs subtypes, with melanoma patients exhibiting higher risk for multiple cirAEs subtypes. However, there was significant variability in the quality of reporting for these risk factors, emphasizing the need for improved consistency and accuracy in data reporting. Conclusions: A variety of demographic, clinical, and biomarker-related factors contribute to the development of cirAEs. Characterizing these risk factors can address clinical needs for cirAE identification, while further mechanistic studies are needed to enhance management strategies. However, there is a limited amount of high-quality prospective evidence on these risk factors, and the quality of reporting on immunotherapy-related adverse events is inconsistent. Future research should focus on validating clinically valuable risk factors and interrogating mechanisms underlying cirAEs emergence.