Real-world Experience with Ipilimumab in Combination with Nivolumab in Advanced Sarcoma: A Retrospective Analysis Including Ultra-Rare Sarcomas.

BACKGROUND: Patients with locally advanced or metastatic sarcoma have a poor prognosis and limited efficacious treatment options. Phase 2 trials have demonstrated efficacy for the combination of ipilimumab and nivolumab in select sarcoma histologies, but real-world data is limited. METHODS: In this single-institution retrospective analysis, patients with metastatic or unresectable sarcoma treated with the combination of immune checkpoint inhibitors (ICI) ipilimumab and nivolumab were assessed for response by iRECIST criteria and were correlated with clinical outcomes. The Kaplan-Meier method was used for survival analysis. RESULTS: From 2019-2024, 90 patients with advanced sarcoma were treated with combination ICI and were evaluable for outcomes. The observed objective response rate (ORR) was 16.7% with clinical benefit rate (CBR) of 30%. The best response was PR in 14.4%, SD in 23.3%, and PD in 62.2%. Median overall survival (OS) (95% CI 14.4-NE months) and mPFS (95% CI 9.6-NE months) were not reached for patients achieving an objective response. Overall survival was superior in patients who experienced irAEs. Both mPFS and mOS were superior in patients with thyroid irAEs. Highest ORR were seen in angiosarcoma, MPNST, leiomyosarcoma, undifferentiated pleomorphic sarcoma, and chondrosarcoma. CONCLUSIONS: Real-world analysis of combination ICI in a large cohort of heavily pretreated patients with advanced sarcomas demonstrates clinical benefit in a meaningful number of patients, including historically unresponsive histologies, though predictive factors remain elusive. The development of irAEs, specifically thyroid dysfunction, was associated with improved survival. Sustained responses were observed in patients who achieved an objective response.