Ten-year outcomes after initial response to immune checkpoint inhibitors in patients with advanced Merkel cell carcinoma

BACKGROUND Immune checkpoint inhibitors (ICIs) have transformed the treatment of advanced Merkel cell carcinoma (MCC) with response rates up to 60% in the 3 pivotal trials (KEYNOTE-017, JAVELIN Merkel-200 and CheckMate-358). However, long-term outcomes, including response durability and survival, remain unclear due to limited follow-up periods in these trials. METHODS We conducted a single-center retrospective study of 30 patients with advanced MCC who received ICIs through one of these 3 trials. In patients with an initial response to trial ICI, we analyzed the duration of response (DOR) and MCC-specific survival (MSS). For patients who progressed after their initial response, salvage therapies and subsequent outcomes were evaluated. RESULTS Twenty of 30 patients (67%) experienced an objective response to the trial ICI regimen (9 – pembrolizumab, 5 – avelumab, 3 – nivolumab and 3 – ipilimumab plus nivolumab). In this cohort of 20 responders, median follow-up was 10.8 years [range, 1.8–11.1]. Median DOR was 6.1 years [95% CI, 2.8–not reached]. Ten patients (50%) remained progression-free. Among the 10 progressing patients, 3 achieved durable disease control with salvage therapies. The 10-year MSS estimate was 70% [95% CI, 49-88%]. There were 7 deaths total (6 MCC-related and 1 from non-MCC comorbidity). CONCLUSIONS ICI-induced responses in patients with advanced MCC can be highly durable, extending beyond 10 years in ~50% of responders and leading to long-term survivorship. However, acquired resistance to ICIs is not infrequent, warranting long-term surveillance. Salvage therapies can provide prolonged benefit in a subset of progressing patients.