54Therapeutic Targeting of IDHl Mutations in Intrahepatic Cholangiocarcinoma Arising in Oilier Disease
Monica Hsiang, Mohamed Nuh, Ronan Mclaughlin, Veronica Cox, Tin-Yun Tang, Ian Hu, Shubham Pant, Jennifer Knox, Milind Javle, Sunyoung LeeAbstract
Background
Ollier disease is a rare, non-hereditary skeletal disorder characterized by multiple enchondromas and somatic IDHI mutations. With a prevalence of ∼1 in 100,000 and typical onset in childhood, Oilier disease is associated with increased malignancy risk, particularly chondrosarcoma. Intrahepatic cholangiocarcinoma (iCCA) in this setting is extremely rare and not well described. IDHl mutations are found in ∼20% of sporadic iCCA, but the clinical presentation and treatment outcomes of IDHl-mutated iCCA in Ollier disease remain unknown.
Methods
We report a retrospective study of three patients with Oilier disease who developed IDHI-mutated iCCA. Clinical, histopathologic, and molecular data were reviewed. Treatment regimens, including use of ivosidenib, a selective IDHI inhibitor, and associated outcomes were analyzed.
Results
All patients were diagnosed with iCCA between ages 25-45, notably younger than the typical median age of 67. Histopathology showed moderately to poorly differentiated adenocarcinoma with dense desmoplastic stroma. With regards to radiologic bony disease, enchondromas presented as calcified expansile lesions that could mimic bony metastases. All tumors harbored an IDHI Rl32C mutation. Prior platinum-based chemotherapy was used in all cases. lvosidenib was administered either as monotherapy or in combination with cytotoxic agents (FOLFOX or gemcitabine/cisplatin). Progression-free survival (PFS) on ivosidenib ranged from 3 to 7 months, consistent with ClarIDHy trial results. Treatment was well tolerated, with no unexpected adverse events.
Conclusions
This is the first retrospective study of lDHl-mutated iCCA in the setting of Ollier disease. Our findings support the feasibility and tolerability of IDHl-targeted therapy in this population, with comparable efficacy to that seen in sporadic IDHl-mutant iCCA. Desmoplastic histology and early age of onset may be distinguishing features. Notably, enchondromas may mimic bone metastases radiographically, posing diagnostic challenges.