Treatment of advanced mucosal melanoma in the immunotherapy era: A joint institutional case series.

Abstract

e21503 Background: Treatment pathways for malignant melanoma have changed dramatically in recent years, with the advent of immunotherapy. Mucosal melanoma is a rare subtype, representing 1-2% of melanomas in Caucasians, with higher incidence reported in other populations. They commonly present at an advanced stage due to their occult, UV naïve location. Rarity limits adequate trial exposure and the literature offers contradictory data on the benefits of immune checkpoint inhibitor (ICI) therapy in this group. Methods: Patient databases at two specialised treatment centres were searched to identify all patients with mucosal melanoma treated with ICI therapy between 01.10.15 and 30.09.19. All patients were reviewed at the regional multi-disciplinary team meeting. Patient demographics, pathology reports, mutation status, stage at start of treatment and prior treatment modalities were noted. Results: Ten patients were identified with a median age 73 years (range 32-80) and M:F ratio of 4:6. The site of the primary cancer was head and neck in 5 cases, gastrointestinal in 3 cases and genitourinary in 2 cases. All patients were BRAF wild type. C-Kit was wild type in 3 patients tested. The median number of cycles of first line ICI was 5.5 (range 1 – 45). At first radiological assessment 7 patients had progressive disease (PD), 2 patients had stable disease and one patient had a complete response (CR). Two patients progressed to second line therapy with a second ICI. One of these demonstrated a partial response after a further 9 months of treatment and had a progression-free survival (PFS) of 30.1 months on second line treatment. One patient received 3 cycles of dual ICI therapy (ipilimumab/nivolumab) but demonstrated PD after 1.5 months. The longest surviving patient currently has a PFS of 43 months. He achieved a CR after just 3 months of pembrolizumab and completed a total of 18 cycles before switching to surveillance. Conclusions: The joint institutional case series demonstrates a poor response to ICI therapy in the majority of patients, yet as commonly reported, response when it occurs can be remarkable. Recent studies have shown increased overall response rate when anti-vascular endothelial growth factor therapies are added to cytotoxics or ICI. Further investigation of this rare subtype is required to identify predictive biomarkers of response to ICI therapy and other targeted and combination treatments.