Clinical and molecular response to vorasidenib in post-transplant patient with IDH2-mutant intrahepatic cholangiocarcinoma

BACKGROUND: IDH2 mutations occur in a small subset of intrahepatic cholangiocarcinoma and currently lack approved targeted therapies. CASE PRESENTATION: We report a post-transplant patient with IDH2-mutant intrahepatic cholangiocarcinoma who developed recurrent disease following multiple treatments for hepatocellular carcinoma and subsequent liver transplantation. Comprehensive genomic profiling revealed an IDH2 p. R172K mutation. Given limited treatment options and contraindications to immunotherapy, off-label treatment with the dual IDH1/2 inhibitor vorasidenib was initiated. RESULTS: The patient achieved a durable radiographic and molecular response, with a reduction in circulating tumor DNA and a partial response by RECIST criteria sustained for approximately 1 year. CONCLUSION: This case highlights the potential clinical relevance of IDH-directed therapy in IDH2-mutant cholangiocarcinoma and demonstrates feasibility in an immunosuppressed post-transplant setting. These findings are hypothesis-generating and support further evaluation of IDH inhibition in this population.