R. G. Cabrejo1, S. Persing1, W. Ibrahim1, K. Olino1, A. Galan1, J. Clune1 1Yale University School Of Medicine,Yale Department Of Surgery,New Haven, CT, USA
Introduction:
Subungual melanoma represents a rare subtype of acral melanoma that typically presents as a dark pigmented stripe or irregular lesion under the nail plate. This subtype carries a poorer prognosis, as it is frequently misdiagnosed, leading to a delay in diagnosis. Subungual melanoma is traditionally treated with amputation of the involved digit or wide local excision. Advances in immunotherapy have been shown to be effective in increasing overall survival in patients with metastatic cutaneous melanoma. It has also been hypothesized that the efficacy of checkpoint inhibitors is linked to the high mutation burden of cutaneous melanoma. To date, the effect of immunotherapy on overall survival in patients with subungual melanoma has not been studied. We hypothesize that patients treated with immunotherapy would have increased overall survival compared to those patients not treated with immunotherapy and therefore would have a high mutation burden.
Methods:
From 1991 to 2018, 65 patients with subungual melanoma who underwent treatment at Yale New Haven Health System were retrospectively identified. Dermatopathology reports, sentinel lymph node biopsy (SLNB) results, demographics clinical outcomes, and overall survival were recorded for all patients. Of the total with stage 3 or 4 melanoma, 19 were not treated with a checkpoint inhibitor and 10 treated with a checkpoint inhibitor after surgical management. These subsets of patients were analyzed using a Kaplan-Meier survival estimates comparing survival of patients treated with immunotherapy to those without. All statistics were performed using STATA 15.0. Tumor and blood samples were also whole genome sequenced and compared to determine somatic mutations.
Results:
Subungual melanoma had a recurrence rate of 46% in our cohort. The average age at diagnosis was 62.6 (± 15.9) years. The average depth of the subungual melanoma was 4.0 (± 2.6) mm. The Cox Regression calculated for age at diagnosis the hazard ratio (HR) is age has a hazard ratio of 1.04 (p=0.20, CI=0.98-1.09), depth has a hazard ratio of 0.79 (p=0.07, CI=0.61-1.01), and checkpoint inhibitors have a hazard ratio of 2.91 (p=0.19, CI=0.58-14.42, β=0.91). The tumor mutation burden was 63.0 (±31.6).
Conclusion:
Immunotherapy is a promising option for management of melanoma, however there are few studies examining its effect in subungual melanoma. Our results suggest that checkpoint inhibitors do not affect survival with an adequate calculated power of 0.91. Subungual melanoma has a low mutation burden of 63.0 (±31.6) compared to cutaneous melanoma, which ranges about 104. Therefore, it may be possible that low efficacy of checkpoint inhibitors in increasing the survival of subungual melanoma may be due to a low mutation burden. Larger randomized controlled trials are needed to help elucidate the effect of immunotherapy on overall survival in subungual melanoma patients.