Combination ipilimumab/nivolumab for refractory Merkel cell carcinoma: A single-institution experience.

Abstract

e21528 Background: Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine tumor with an aggressive disease course. Many patients will recur or progress following resection and first-line systemic therapy, and salvage therapy options are limited. Recent studies evaluating combination ipilimumab/nivolumab (ipi-nivo) as second-line therapy for refractory/advanced MCC have found mixed results, and the standard-of-care for this patient population is not yet defined. Given the lack of consensus on ideal regimens for refractory disease, we report our institutional experience with combination ipi-nivo. Methods: In this retrospective analysis, we reviewed the electronic medical record at the Hospital of the University of Pennsylvania from 2015 – 2025 for patients with MCC who had progressive/recurrent disease following first-line therapy (surgery ± chemotherapy, radiation, and/or immunotherapy) who were treated with ipilimumab 3 mg/kg and nivolumab 1 mg/kg. Objective treatment responses to ipi-nivo were determined at regular intervals based on Response Evaluation Criteria in Solid Tumors Version 1.1. The primary outcome was objective response rate (ORR), and secondary outcomes were progression-free survival (PFS) and toxicity profile. Survival estimates were calculated using the Kaplan-Meier method. Results: A total of 17 patients met inclusion criteria, of which 13 (76%) were male; median age at initiation of ipi-nivo was 70 years (interquartile range [IQR] 66 – 74). Four (24%) patients achieved a complete response (CR) and 2 (12%) achieved partial response (PR), with an ORR of 36%. Two patients were immunotherapy-naïve prior to initiating ipi-nivo and of these, 1 patient had PR. Median duration of response (DOR) was 6.6 months (IQR 4 – 14). At the latest follow-up period, of the patients that had objective response to ipi-nivo, 1 patient died of other causes and 5 patients had sustained response. Median PFS was 2.8 months (95% confidence interval [CI]: 0.9 – NR) at median follow-up of 12 months. Estimated 1-year PFS was 34.3% (95% CI: 13 – 57) and 1-year overall survival (OS) was 63.3% (95% CI: 36 – 82). In the overall cohort, 8 (47%) patients were still alive at latest follow-up. Grade 3/4 immune-related adverse events (irAE) occurred in 3 (18%) patients, of which 2 patients had to permanently discontinue therapy. Conclusions: Our single-institution experience adds to the currently limited body of literature for refractory MCC, suggesting that ipi-nivo is a viable strategy with durable response rates and a tolerable toxicity profile. Outcomes for patients receiving ipi-nivo for refractory MCC (n = 17). ORR, n (%) 6 (36) CR, n (%) 4 (24) PR, n (%) 2 (12) SD, n (%) 2 (12) PD, n (%) 9 (53) Median DOR, m (IQR) 6.6 (4 – 14) Median PFS, m (95% CI) 2.8 (0.9 – NR) 1-year PFS, % (95% CI) 34.3 (13 – 57) 1-year OS, % (95% CI) 63.3 (36 – 82) Grade 3/4 irAE, n (%) 3 (18) SD – stable disease, PD – progressive disease, NR – not reached, m – months.