Real-World Outcomes for Patients with Clinically Node-Positive Melanoma Undergoing Neoadjuvant Immunotherapy and Nodal Dissection.

[BACKGROUND] Neoadjuvant immunotherapy (nIO) followed by a therapeutic lymph node dissection (TLND) for patients with clinically node-positive melanoma is supported by level 1 evidence. Our aim was to assess the association of pathologic response (PR) and nIO regimen with survival among patients with clinical stage III melanoma undergoing nIO and TLND.

[METHODS] Our study included patients treated with nIO followed by a TLND from a large academic institution between 2016 and 2024. The pathologic response was assessed using established guidelines. Differences in extent of PR by nIO regimen were examined. Disease-free survival (DFS) and overall survival (OS) by PR and nIO regimen were assessed.

[RESULTS] The study included 121 patients (78.5% treated with combination nIO; 21.5% treated with single-agent anti-PD-1). The pCR rate was 64.2% for combination therapy and 53.8% for monotherapy (P=0.11). In univariable analysis, patients who received combination therapy had a 2-year DFS similar to patients treated with single-agent anti-PD-1 (86.5% vs 85.1%, respectively; P=0.43). Patients with a pCR had a 2-year DFS of 94.4% versus 57.3% among those with pathologic non-response (pNR) (P<0.001). In multivariable analysis, PR was associated with DFS, but the nIO regimen was not. Our findings showed similar results for OS, with a 2-year OS of 98.1% for patients with pCR compared with 94.7% for those with pNR (P=0.01).

[CONCLUSIONS] Consistent with clinical trial data, the findings in this study support PR as a strong predictor of survival in this patient population. Studies investigating the de-escalation of surgical and systemic treatment based on PR as well as biomarkers of patients who can achieve a pCR after monotherapy alone are warranted.