EXTH-77. INFANT-TYPE HEMISPHERIC GLIOMAS WITH INITIAL RESPONSE FOLLOWED BY RESISTANCE ON TARGETED AGENTS

Abstract Pediatric-type Diffuse High Grade Gliomas (pHGG) are a rare brain tumor with high mortality and need for more effective treatment options. pHGG’s make up only about 10% of CNS tumors but are responsible for a majority of the deaths. Infant-type Hemispheric Gliomas are a subtype of pHGG with tyrosine kinase alterations in genes such as ROS1, ALK, MET, and NTRK1-3. Despite advances in categorization and targeted therapies, the natural history of patients with infant HGG treated with targeted therapy over time needs to be better characterized, including the durability of objective responses. We present a retrospective case series involving two patients diagnosed with Infant-type Hemispheric Gliomas at Arkansas Children’s Hospital from 2022-2024. Each diagnosis was determined based on histology, targeted tumor sequencing, and methylation profiling. Both patients were initially treated with primary surgical resection and systemic chemotherapy. Each patient experienced disease progression. Actionable pathogenic mutations were identified in both patients (a MET alteration in patient 1 who was then started on Cabozantinib, an ALK fusion in patient 2 subsequently treated with Lorlatinib) with an objective disease response in both patients. In both cases, further relapse occurred while on targeted inhibition. Relapse specimen was not available for patient 1, but for patient 2, recurrent tumor sequencing revealed similar genetics from the diagnostic specimen except for a MET copy number gain suggesting the mechanism of resistance in this patient. Infant-type Hemispheric Gliomas with targetable alterations can show meaningful responses to pathway inhibition. Relapse after initial response may warrant additional surgical sample to identify new alterations which can lead to changes in therapy. Larger prospective cohorts are needed to study targeted agents in this population, and early integration during radiation or after initial diagnosis may be needed.