MDM2, MDM4 and EGFR Amplifications and Hyperprogression in Metastatic Acral and Mucosal Melanoma.

Background: Mucosal and acral melanoma respond worse to immune checkpoint inhibitors (ICI) than cutaneous melanoma. as well as amplifications are supposed to be associated with hyperprogression on ICI in diverse cancers. We therefore investigated the response of metastatic acral and mucosal melanoma to ICI in regard to or amplifications and melanoma type.

Methods: We conducted a query of our melanoma registry, looking for patients with metastatic acral or mucosal melanoma treated by ICI. Whole exome sequencing, FISH and immunohistochemistry on melanoma tissue could be performed on 45 of the total cohort of 51 patients. Data were correlated with patients` responses to ICI and survival.

Results: 22 out of 51 patients had hyperprogressive disease (an increase in tumor load of >50% at the first staging). Hyperprogression occurred more often in case of or amplification or <1% PD-L1 positive tumor cells. Nevertheless, this association was not significant. Interestingly, the anorectal melanoma type and the presence of liver metastases were significantly associated with worse survival.

Conclusions: So far, we found no reliable predictive marker for patients who develop hyperprogression on ICI, specifically with regard to or amplifications. Nevertheless, patients with anorectal melanoma, liver metastases or melanoma with amplified seem to have an increased risk of not benefitting from ICI.