Abstract IA16: The landscape of mucosal melanoma: A long way to go
Authors: Guo Jun 
Published: June 2022

Mucosal melanoma is a rare disease, accounting for approximately 1.4% of all Caucasians’ melanomas and 22% of Asian melanomas, which are commonly found in the nasal cavity or sinuses, anorectum, and vulvovagina. Nearly half of the mucosal melanomas are amelanotic. The most common sites of metastatic disease are the liver and the lungs. The prognosis may be similar regardless of anatomic site of origin. The genetics of mucosal melanoma thatg originates from melanocytes within mucosal epithelia has not been fully explored. Data suggest BRAF may occur in only 3–15% of all cases of mucosal melanoma. Mutations in KIT can be identified in 7–17% of all patients with mucosal melanoma. As to the adjuvant therapy, the only published randomized evidence supporting adjuvant therapy after resection of mucosal melanoma was from Lian et al. They randomized 189 patients with resected mucosal melanoma to observation, 1 year of high-dose IFN-α2b, or thrice-weekly chemotherapy with temozolomide plus cisplatin for six cycles. Adjuvant therapy was associated with a trend toward improved survival and HDI was less effective than temozolomide-based chemotherapy for patients with resected mucosal melanoma in respect to RFS. The preliminary interim analysis of a phase III trial (NCT03435302) of 204 patients with mucosal melanoma comparing temozolomide-based chemotherapy with HDI showed that the chemo was superior to HDI. Several clinical trials on adjuvant therapy of mucosal melanomas are ongoing, including NCT03178123 (a phase III trial of PD-1 inhibitors VS HDI) and NCT03241186 (phase II trial of nivolumab + ipilimumab). The clinical trials for systemic treatment of unresectable or metastatic mucosal melanoma were limited. A pooled analysis of the outcomes of patients with metastatic mucosal melanoma treated in trials either with single-agent nivolumab or the combination of ipilimumab and nivolumab compared outcomes to those of patients with cutaneous melanoma. The ORR for mucosal melanoma receiving nivolumab monotherapy or nivolumab combined with ipilimumab were lower than cutaneous melanoma, 23.3% vs. 40.9%, 37.1% vs. 60.4%. PD-1 monoclonal antibody was less effective in mucosal melanomas maybe because of low PD-L1 expression and tumor mutation burden (TMB). At the 2018 ASCO meeting, the results of phase II study of JS001 (PD-1 inhibitors) were reported. 128 melanoma patients were enrolled. Subgroup analysis showed that patients with mucosal origin were less effective (mucosal 0%). How to increase the efficacy for the mucosal melanoma? As we all know, liver metastases are common in mucosal melanomas and difficult to handle. A phase Ic study of oncolytic virus (OrienX010) injected into liver metastases demonstrated good tolerance and efficacy in Chinese patients. The next step is to combine oncolytic virus injected into liver lesions with PD-1 antibody to improve the efficacy of liver metastasis. On the other hand, TKIs are found to have an influence on microenvironment in tumor and facilitate immunotherapy. We conducted a phase Ib study of JS001 in combination with axitinib in metastatic mucosal melanoma. The results were reported in ASCO 2018, which were encouraging to achieve ORR of 66.7%. Recurrent activating mutations in KIT have been identified in 15% of patients, but KIT inhibitors have not produced durable clinical responses. Patients with mucosal melanoma have a poor prognosis in part due to the lack of targeted therapies. Imatinib may remain the first-choice treatment option for patients with a KIT mutation. For mucosal melanoma patients, there is still a long way to go.

Citation Format: Jun Guo. The landscape of mucosal melanoma: A long way to go [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr IA16.