Real-world analyses of first-line immune checkpoint inhibitors in unresectable Merkel cell carcinoma.

e21597 Background: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer of the elderly. Immune checkpoint inhibitors (ICI) are now the first-line treatment for unresectable MCC. However, elderly patients may be particularly vulnerable to the consequences of immune-related adverse events (irAEs). We retrospectively analyzed the efficacy and safety of ICIs in unresectable MCC at OSUCCC. Methods: We reviewed the electronic medical records of patients treated for MCC from 01/01/2010 to 04/30/2024. Major outcomes of interest are tumor response, overall survival (OS), and safety profiles. Chi-square test and Kaplan-Meier (log-rank test) were used. Results: Treatment outcomes were assessable in 41 patients with unresectable MCC. Thirty-two received ICI and 9 other therapies in the first line. Pembrolizumab was the most frequent ICI in 12 patients, followed by nivolumab in 11, ipilimumab-nivolumab (ipi/nivo) in 7, and avelumab in 2. The objective response rate was 78.1% in the ICI group, superior to 66.7% in the non-ICI group (see Table 1). Upfront ipi/nivo achieved 85.7% complete response (CR) with 1 stable disease (SD). Six patients received ipi/nivo after first-line mono-ICI failed, with 2 achieving partial response (PR). Median follow-up was 17.2 months. Median OS in the ICI group was 26.1 (95% CI 28.8-53.8) months, superior to 16.4 (95% CI 12.2-17.8) months in the non-ICI group (HR: 0.14 [0.04-0.47], P = 0.001). In terms of the number of treatment cycles completed in the ICI group: 3 patients completed 1-2; 11, 3-5; 6, 6-10; 8, > 10; and 4 are still receiving ICI. The median ICI therapy duration was 5.9 (95% CI 5.8-13) months. The incidence of ICI-related irAEs that required steroids was 21.9% (7/32), including colitis (12.5%, 4/32). The most common causes for ICI discontinuation were treatment course completion, disease progression, and irAEs. Conclusions: First-line ICI therapy is highly effective in unresectable MCC with superior survival benefits. ICIs are well tolerated by most elderly patients with MCC. Longer follow-up and a larger cohort will help us better understand ICI therapy's role in this disease. Patient characteristics & tumor response. ICI Group ( n =32) Non-ICI Group ( n =9) Average Age (years)* 74.9 69.6 Gender* Male 19 (59.4%) 4 (44.4%) Female 13 (40.6%) 5 (55.6%) Clinical Stage* III 14 (43.8%) 5 (55.6%) IV 18 (56.2%) 4 (44.4%) Tumor Response+ CR 17 (53.1%) 0 PR 8 (25.0%) 6 (66.7%) SD 2 (6.3%) 2 (22.2%) PD 5 (15.6%) 1 (11.1%) * P >0.05 and + P <0.05 between ICI/non-ICI groups.