Predictive factors of hepatotoxicity in immunotherapy with checkpoint inhibitors in patients treated for melanoma and kidney cancer

Introduction. Checkpoint inhibitors immunotherapy (CPI) is widely used in the treatment of malignant tumors and has a positive effect on patient prognosis. CPI treatment is associated with various immunological adverse events (AEs), including a rare one - immunological hepatitis. Material and methods. This study aims to analyze hepatic AEs in patients undergoing CPI therapy and to attempt to determine hepatotoxicity predictors. A retrospective statistical analysis of medical records of 223 CPI patients treated in the years 2014-2021 in Lower Silesian Oncology, Pulmonology and Hematology Center in Wroclaw was performed. Results. Toxicity grade 1-4 according to the Common Terminology Criteria for Adverse Events (CTCAE) occurred in 26% of patients, of which 6% were grade 3-4. An increased risk of hepatotoxicity was found in the group of patients <= 60 years of age compared to the > 60-year-old group (34.1% vs. 21.7%, p = 0.0418). It has also been confirmed that the occurrence of hepatic AEs during first-line immunotherapy increases the risk of toxicity recurrence during second-line immunotherapy (58.3% vs. 15.4%, p = 0.0199). No significantly increased risk of hepatic AEs has been demonstrated in patients with liver metastases, hepatic steatosis, or other chronic liver disease, or in patients after chemotherapy, with elevated baseline levels of lactate dehydrogenase (LDH), or increased body mass index (BMI). Conclusions. The hepatotoxicity of CPI immunotherapy poses a significant diagnostic and therapeutic challenge. Its early detection and treatment according to the recommended algorithms increases patient safety for patients and sometimes allows the continuation of treatment.