No abstract

A djuvant immune checkpoint inhibition (CPI) and BRAF/ MEK-targeted therapies after therapeutic lymph node dissection (TLND) have improved relapse-free survival (RFS) in patients with clinical stage III nodal melanoma. Despite these improvements, approximately 40-50% of patients have a relapse within 3-5 years after TLND 1-3 . Preclinical and early clinical trial data suggest that neoadjuvant CPI leads to superior anti-tumor immunity and survival benefit compared to adjuvant CPI 4,5 . Similarly to stage IV melanoma, the combination of anti-CLTA-4 and anti-PD-1 appears to be superior to anti-PD-1 monotherapy in the neoadjuvant setting 6,7 . Previous clinical trials (OpACIN (NCT02437279) and OpACIN-neo (NCT02977052)) testing neoadjuvant ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) in stage III melanoma demonstrated high pathologic response rates (pRRs; 74-78%) and a strong association between pathologic response and RFS, with 94-100% of responding patients remaining free of relapse at 2 years 5,7-9 . Similarly, long-term benefit was observed upon complete response to CPI in stage IV melanoma, even after cessation of CPI [10][11][12] .The association between response and survival; the observed ongoing responses after cessation of therapy in stage IV melanoma; and the substantial morbidity from TLND [13][14][15][16] that impairs