Safety and efficacy of immune checkpoint inhibitor rechallenge in metastatic fumarate hydratase-deficient renal cell carcinoma: A retrospective study.

• DOI: 10.1200/jco.2025.43.5_suppl.500
• Publication Date: 2025-02-18T14:38:27Z
• Authors: Yanfeng Tang; Minghao Wang; Jiayu Liang; Hao Zeng
• Keywords: Immune checkpoint; Kidney cancer; Fumarase

500 Background: Fumarate hydratase–deficient renal cell carcinoma (FH-deficient RCC) is a rare subtype of kidney cancer characterized by FH-inactivating alterations. Studies have revealed highly immunogenic features in this lethal disease, providing molecular evidence for implement immune checkpoint inhibitor (ICI). Due to the nature FH-deficient RCC, significant proportion patients continue disease progression after receiving ICI combination therapy (ICI plus tyrosine kinase inhibitors, TKI). Herein, we aim evaluate safety and efficacy rechallenge metastatic fumarate hydratase-deficient real-world settings. Methods: A multicenter database diagnosed with identified through IHC negative FH and/or positive 2SC, was explored. The study enrolled RCC who received within three months discontinuing prior treatments between January 2018 July 2023. Results: total 18 patients, each at least two lines therapy, were included study. majority (n=15) experienced following prior-line immunotherapy. Among these, 66.7% (10/15) showed original lesions, while 33.3% (5/15) developed new lesions. Three transitioned later-line immunotherapy due immune-related adverse events (irAEs) grade 3 or higher. incidence 1-2 irAEs comparable therapies (28.15% vs. 27.30%, p=0.8932), as higher (0.86% 0.29%, p=0.594). For entire cohort, median progression-free survival (mPFS) 16.2 (95% CI: 5.565-26.835 months), mPFS 15.2 3.915-26.485 months). objective response rate (ORR) control (DCR) 17% 78%, respectively, compared an ORR 28% DCR 67% therapy. Conclusions: This cohort demonstrated that achieved favorable profile RCC. Therefore, resumption may be viable option managing