Abstract 1111P
Background
Immune checkpoint inhibitor (ICI) has greatly improved the prognosis of advanced melanoma. However, the efficacy of ICI in Japanese patients has been found to be lower than Caucasian. It is thought that one of the causes is that acral and mucosal melanoma have a low tumour mutation burden and driver mutations such as BRAF. However, there is no report performing the genomic and transcriptomic analysis in Japanese patients. By analysing the Japanese patients with melanoma, we aimed to clarify how they differ from Caucasians. Furthermore, we challenged to explore biomarkers for the efficacy of ICI.
Methods
The blood and tumor samples were collected from the patients before and after ICI therapy at multiple facilities. Based on the clinical information, the genomic and transcriptomic analysis were performed. In particular, ICI responder and non-responder genomes were analyzed separately.
Results
In this analysis, 129 tumor samples from 78 cases were collected, and 112 tumors and 65 cases were analyzed. Somatic mutations in Japanese patients are significantly different from those in Caucasians. That is, there were few mutations such as single nucleotide variant and single base substitution, and the majority were triple wild type tumours without driver mutations such as BRAF. While the presence of these mutations is associated with treatment response in the Caucasian patients, the involvement of these mutations was found to be less significant in Japanese patients. In this context, we compared the gene expressions of responder and non-responder tumours and found differences in genes such as HLA-A24, follicular helper T cells, and MARCO. We considered that these genes might be potential biomarkers in Japanese melanoma.
Conclusions
This is the first and largest study in Japan in which tumour samples were prospectively analysed before and after ICI treatment for melanoma. Further studies focusing on these biomarkers are desirable.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Japan Agency for Medical Research and Development.
Disclosure
All authors have declared no conflicts of interest.
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