Abstract: Background and purpose: Immune checkpoint inhibitor (ICI) has become an important means of tumor treatment. However, their significant effects are accompanied by drug-related adverse reactions. This study aimed to observe the safety of pembrolizumab in patients with advanced melanoma, and to explore the clinical predictive factors for adverse events risk and the correlation between adverse events and responses with anti-programmed death-1 (PD-1) monoclonal antibodies. Methods: The clinical data of 54 patients who were enrolled in a phase Ⅰb study of pembrolizumab as a second-line treatment for Chinese patients with advanced or metastatic melanoma (KEYNOTE-151) were collected at the Peking University Cancer Hospital from Aug. 2016 to Jul. 2017. Clinical information included gender, age, metastatic stage, primary site, previous chemotherapy history, Eastern Cooperative Oncology Group (ECOG) score, blood laboratory tests, adverse events and treatment outcome. The occurrence of adverse events was analyzed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grading scale. The response was calculated based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results: The rate of adverse events was 88.9% (48/54) in patients with advanced melanoma treated with pembrolizumab, and the rate of serious adverse events was 13.0% (7/54). There was no death. Hepatotoxicity was the main cause of interruption and discontinuation of medication. We failed to show an association between both of the clinical features and blood cell count and occurrence of serious adverse events, while vitiligo (P=0.001) and thyroid dysfunction (P=0.007) were significantly associated with better response. Conclusion: Although pembrolizumab has a higher incidence of adverse reactions in advanced melanoma, they are generally grade 1-2 with better tolerance. Hepatotoxicity has the most significant effect on the study drug. Vitiligo and thyroid dysfunction may both be predictive factors of better efficacy in patients receiving PD-1 monoclonal antibodies.

Key words:  , Melanoma, Pembrolizumab, Programmed death-1, Monoclonal antibody, Adverse events