Assessment of Variables Related to the Risk of Severe Adverse Events in Cutaneous Melanoma Patients Treated with Immune Checkpoint Inhibitors

Simple Summary Malignant melanoma is an aggressive cancer with a globally increasing disease rate. Historically, overall survival has been less than one year for advanced disease with distant metastases. The implementation of immune checkpoint inhibitors has remarkably transformed the therapeutic landscape, yielding 40% to 50% five-year survival rates. However, this improvement comes with a cost, as more than 50% of patients may experience severe side effects. Since there is a lack of validated markers predicting a high risk of severe immune therapy-related side effects, we conducted a systematic literature review to investigate the association between patient baseline characteristics and the risk of serious side effects from immune checkpoint blockade. The highest risk was identified among patients treated with ipilimumab. Yet, available data were insufficient to calculate patient-specific risk for adverse events. This work displays the need to report information about side effects more explicitly.Abstract Malignant melanoma is a prevalent and aggressive cancer, with globally increasing incidences. While immune checkpoint inhibitors (ICIs) have prolonged the survival of patients with advanced melanoma over the last decade, this improvement comes with the risk of severe immune-related adverse events (irAEs). This systematic review investigates patient baseline characteristics (BCs) as predictive factors for developing severe gastrointestinal, hepatic, and pulmonary irAEs in patients treated with ipilimumab (anti-CTLA-4) and/or nivolumab/pembrolizumab (anti-PD-1). A systematic literature search was conducted in the Ovid databases MEDLINE and EMBASE on 22 April 2022, following the PRISMA guidelines. Out of 1694 articles, 13 were included in the final analysis. We analyzed BCs and the occurrence of severe colitis, hepatitis, and pneumonitis in 22 treatment arms and 3 treatment groups: anti-CTLA-4 (n = 2904), anti-PD-1 (n = 1301), or combination therapy (n = 822). However, missing data preclude a direct comparison of individual BCs and the association to specific irAEs between studies. Descriptive analysis did not identify any significant association between median age, gender distribution, or performance status and severe colitis, hepatitis, or pneumonitis for any of the three treatment groups. We call for greater transparency and standardization in the reporting of patient-specific irAEs.