Doctor, am I cured? Characteristics of long-term survivors with advanced melanoma treated with immunotherapy.

Abstract

e21502 Background: Immune checkpoint inhibitors (ICIs) have transformed the prognosis of advanced melanoma, enabling a subset of patients to achieve prolonged survival. The concept of long-term survivors (LTS) raises the question of whether some metastatic patients who respond to immunotherapy may never relapse and could be considered potentially cured. Characterizing this population is relevant to identify predictors of durable benefit. Methods: A total of 244 patients with unresectable stage III or stage IV melanoma treated at Instituto Roffo, University of Buenos Aires, were included. Among them, 156 had a minimum clinical follow-up of 3 years. LTS were defined as patients with an overall survival (OS) ≥36 months. Demographic characteristics, histologic subtype, mutational status, treatment received, objective response, and adverse events were analyzed. Results: Data from 72 patients (46.1% of the 156 with follow-up ≥3 years) were analyzed. Median age was 58 years, and 65% were male. Melanoma subtypes were cutaneous (62%), mucosal (13%), and acral (10%). BRAF mutation was detected in 37 patients (51%). Most patients received immunotherapy as first-line treatment (79%). The most frequently used regimens were anti–PD-1 agents (pembrolizumab or nivolumab) and the combination of ipilimumab plus nivolumab. Best responses included stable disease in 30% (n=11), partial response in 11% (n=24), and complete response in 51% (n=37), with a median treatment duration of 724 days. The most frequent adverse events were vitiligo (n=22), rash (n=9), pruritus (n=11), thyroiditis (n=22), asthenia (n=20), and transaminitis (n=10), mostly grade 1. Eight grade 3 and two grade 4 events (myocarditis and myositis) were reported. The main reasons for treatment discontinuation were toxicity (41%) and planned completion (31%). Median OS and progression-free survival (PFS) in the LTS cohort were 75.6 and 58.9 months, respectively. Conclusions: Nearly half of patients with a follow-up ≥3 years achieved prolonged OS (≥3 years) with immunotherapy, and two thirds remain progression-free. These findings suggest that beyond extending survival, a subset of patients may never relapse and could be considered potentially cured, representing a paradigm shift in the management of advanced melanoma.