Long term survival outcomes of immune checkpoint inhibitors in metastatic melanoma: Later relapse and long-term outcomes beyond 5 years.

Abstract

9556 Background: Immune checkpoint inhibitors (ICI) have improved survival outcomes in patients with metastatic melanoma, with a subset achieving durable long term survival outcomes. However, the incidence of late relapse and outcomes among patients who are alive but not progression-free at 5 years remain unknown. Methods: This is a multi-institutional retrospective study of patients with metastatic melanoma treated with either single agent anti-PD1 therapy or a combination of anti-PD1/CTLA-4 who started treatment prior to January 1, 2016. We analyzed the following outcomes: progression free survival at 5 years, late relapses (defined as progression > 5 years after ICI initiation), sites of late relapse, and long-term overall survival. Results: 206 patients with metastatic melanoma were included; 65% (n = 135) were male. Most patients 86% (n = 177) had cutaneous melanoma and 29% (n = 59) had BRAF V600E/K mutations. In this cohort, 56% (n = 115) received a single agent anti-PD1, while the remaining 44% (n = 91) of patients received a combination of Ipilimumab (IPI) plus anti-PD1. The median follow-up from treatment initiation was 9.1 years. At 5 years, 68% (n = 140) of patients were progression-free. Late relapse, occurring > 5 years after ICI treatment initiation, was seen in 6% (n = 12) of patients, at a median of 8.2 years from ICI treatment initiation. Among 12 patients with melanoma relapses, site of relapses was most commonly at nodal metastases (50%), followed by visceral (17%), brain (17%), and bone/spine (17%), soft tissue (8%), and unspecified sites (8%). Overall, 50% of patients had oligo progression, 33% had metastasis at multiple sites, and 17% unspecified. Following late relapse, 83% (n = 10) were rechallenged with ICI; 50% were rechallenged with the same ICI, 17% switched from IPI plus anti-PD1 to single agent anti-PD1, 17% unspecified, and the other 17% were not rechallenged with ICI. The disease control rate was 75% among patients rechallenged with anti-PD1, 100% among those rechallenged with IPI plus anti-PD1, and 100% among patients who switched from IPI plus anti-PD1 to single agent anti-PD1. At last follow-up, 75% (n = 9) of patients with late relapse were alive. Additional analyses, including Kaplan Meier estimates of progression-free and overall survival and incidence of long term sequalae from immune related adverse events will be reported. Conclusions: In this multi-institutional cohort of long-term survivors with metastatic melanoma, late relapse occurred uncommonly. And the outcomes following late relapses were generally favorable, with many patients still experiencing ongoing survival. The findings in our study support continued long-term surveillance beyond 5 years and provide clear expectations in daily clinical practice regarding cure and survivorship following anti-PD1 based therapy in metastatic melanoma