Adjuvant versus no adjuvant therapy after major pathological response to neoadjuvant immunotherapy in resectable melanoma: A Swedish nationwide population-based study (NEO-MEL).

Abstract

9566 Background: Randomized trials have shown that neoadjuvant PD-1–based immunotherapy improves outcomes compared with adjuvant therapy alone in patients with resectable stage III–IV cutaneous melanoma. In trials, patients experiencing a major pathological response (MPR) rarely relapse, and in the NADINA trial, adjuvant therapy was omitted in this group. However, the need for continued adjuvant treatment after MPR has never been prospectively tested, and real-world evidence is limited. Methods: This population-based cohort study included all patients with macroscopic, resectable cutaneous melanoma treated with neoadjuvant immune checkpoint inhibitor(s) across all academic melanoma centers in Sweden between January 1, 2022 and December 30, 2025. Clinical and pathological data were extracted from medical records. MPR was defined as pathological complete response (pCR) or near-pCR. Recurrence-free survival (RFS) was estimated using the Kaplan–Meier method and differences assessed with log-rank test. Results: A total of 279 patients initiated neoadjuvant treatment; 254 (91%) underwent surgery as planned, and 251 had evaluable pathological assessment. Overall, 103 patients (37%) experienced pCR and 17 (6%) near-pCR, yielding 120 patients (43%) with MPR. At a median follow-up of 19 moths, the estimated 24-month RFS for patients with MPR was 92%. Among MPR patients, 52 (43%) received continued adjuvant immune checkpoint inhibitor therapy, while 68 (57%) received no adjuvant treatment. RFS differed significantly between groups, with estimated 24-month RFS of 96% in patients receiving adjuvant therapy versus 80% in those who did not ( P =0.048). In the non-adjuvant group, there were five recurrences (three had pCR and two had near pCR), two were local recurrences and three were distant metastatic events, compared with no recurrence events in the adjuvant group. One unrelated death occurred in the non-adjuvant group and two unrelated deaths in adjuvant group. Conclusions: In this nationwide real-world cohort, patients experiencing MPR after neoadjuvant immunotherapy had excellent outcomes overall. However, a small but clinically relevant risk of relapse was observed among patients who did not receive continued adjuvant therapy after MPR. These findings emphasize the need for individualized assessment when considering adjuvant treatment in patients with MPR. Longer follow-up is needed to determine whether additional events emerge and, importantly, whether relapses can be effectively salvaged with immune checkpoint inhibitor rechallenge.