Outcomes following long-term disease control with immune checkpoint inhibitors in patients with advanced melanoma

Abstract

Immune checkpoint inhibitors (ICI) can achieve durable responses in patients with advanced melanoma, and results from clinical trials suggest cure may be possible for a subset of patients. Despite clinical trial data, little is known about the risk, character, and clinical outcome of late recurrences after ICI. This study aimed to explore the disease outcomes and survival in a cohort of patients with long-term responses to ICI. We retrospectively identified patients treated with ICI for advanced melanoma with long-term disease control, defined as not requiring a subsequent line of systemic therapy within 3 years of ICI commencement. We analysed disease characteristics, treatment, toxicity, recurrence patterns, management, and outcomes. A total of 567 patients were identified with a median follow-up of 7.1 years: 504 (89 %) without disease progression within 3 years (cohort 1) and 63 (11.1 %) with disease progression within 3 years managed without a change in systemic therapy (cohort 2). Subsequent progression after 3 years occurred for 39 (7.7 %) patients in cohort 1, compared to 14 (22 %) in cohort 2. Predictors for late progression after 3 years were a non-complete radiological response (CR) best response and prior progression within 3 years. Thirty-two patients (5.6 %) died during follow-up, 8 (1.4 %) from melanoma, 6 (1.2 %) from cohort 1 and 2 (3.2 %) from cohort 2. In this population of patients with advanced melanoma with long-term disease control from ICI, the risk of subsequent disease progression and death was low. This suggests that a significant proportion of long-term ICI responders are likely cured and may inform the frequency and duration of follow-up.

Keywords: Checkpoint inhibitors; Immunotherapy; Melanoma; Survival.