Role of Novel Immunotherapy in Recurrent Thick and Ultra-Thick Melanoma
*Joshua Cohen, *Andrew M. Blakely, *Danielle S. Comissiong, Michael P. Vezeridis, Thomas J. Miner
Rhode Island Hospital, Providence, RI
Objective: Thick (≥4mm) melanomas are high-risk for disease progression and failure of surgical monotherapy. We investigated outcomes of advanced melanomas and influence of novel immunotherapies.
Design: Retrospective review of prospectively-maintained database.
Setting: Academic tertiary-care center.
Patients: Adults who underwent wide local excision of thick melanoma, June 2005 to December 2016.
Interventions: Excision, sentinel lymph node biopsy (SLNB), immunotherapy.
Main Outcome Measures: Disease progression, response to immunotherapy.
Results: 103 of 1714 (6%) patients were diagnosed with thick melanoma (≥4mm), of which 41 (39.8%) had an ultra-thick lesion (≥8mm, range 4-39mm). There was no significant difference between thick and ultra-thick lesions in regard to ulceration, mitotic rate, lymphovascular invasion, or performance or positivity of either SLNB or lymphadenectomy. Margins of excision were ≥2 cm in 92.2% of patients. Disease progression or recurrence were identified in 40 patients overall (38.8%). Multivariate analysis determined that progression/recurrence were independently associated with thickness ≥8mm (OR 4.3) and +SLNB (OR 4.8) with local recurrence largely due to intransit disease. Eight patients with recurrence (5 locoregional and 3 distant) received immunotherapy. Median time to recurrence was 163 days. There was no significant difference in type of- or time to- recurrence in patients with +SNLB. High-risk features were present in all patients. Patients received ipilimumab, pembrolizumab, or combination ipilimumab-nivolumab. Median duration of therapy was 258 days. Two patients (25%) had disease progression on immunotherapy with a median time to progression of 51 days.
Conclusions: Thick melanoma disease progression was independently associated with ultra-thick lesions and positive SLNB. Although initial wide local excision provides durable local control, distant and regional progression is common. Immunotherapy may enhance the therapeutic benefits for these patients.