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Published on: May 18, 2018
MDM2, MDM4 and EGFR Amplifications and Hyperprogression in Metastatic Acral and Mucosal Melanoma
Andrea Forschner1, Franz-Joachim Hilke2, Irina Bonzheim3
1Center for Dermatooncology, Department of Dermatology, University Hospital Tübingen, 72076 Tübingen, Germany.
Background:
Mucosal and acral melanoma respond worse to immune checkpoint inhibitors (ICI) than cutaneous melanoma. MDM2/4 as well as EGFR 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 MDM2/4 or EGFR 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 MDM2/4 or EGFR 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 MDM2/4 or EGFR amplifications. Nevertheless, patients with anorectal melanoma, liver metastases or melanoma with amplified MYC seem to have an increased risk of not benefitting from ICI.
Insights
This study found no reliable markers for predicting hyperprogression in mucosal and acral melanoma patients treated with immune checkpoint inhibitors (ICI). Anorectal melanoma and liver metastases were linked to poorer survival outcomes in advanced melanoma.
Area of Science:
- Oncology
- Immunotherapy
- Genetics
Background:
- Mucosal and acral melanomas exhibit poorer responses to immune checkpoint inhibitors (ICI) compared to cutaneous melanoma.
- Gene amplifications in MDM2/4 and EGFR are implicated in hyperprogression during ICI therapy across various cancers.
Purpose of the Study:
- To investigate the response of metastatic acral and mucosal melanoma to ICI.
- To evaluate the association between MDM2/4 or EGFR amplifications, melanoma type, and ICI response.
Main Methods:
- Retrospective analysis of metastatic acral and mucosal melanoma patients treated with ICI.
- Utilized whole exome sequencing, FISH, and immunohistochemistry on tumor tissues.
- Correlated genetic alterations and clinical data with patient response and survival.
Main Results:
- 22 out of 51 patients (43%) experienced hyperprogressive disease.
- No significant association was found between MDM2/4 or EGFR amplification and hyperprogression.
- Anorectal melanoma type and liver metastases were significantly associated with worse survival.
Conclusions:
- Currently, no definitive predictive marker for ICI-induced hyperprogression in acral/mucosal melanoma has been identified.
- Anorectal melanoma, liver metastases, and MYC amplification may indicate an increased risk of poor response to ICI therapy.
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