ID #290 Dramatic response to Crizotinib in a MET fusion positive pediatric glioma

Abstract

Receptor tyrosine kinase (RTK) fusions involving MET is reported in 3 to 10% of infant high-grade gliomas and has been increasingly recognized as potential therapeutic targets. We report a 22-month-old girl diagnosed with a large deep-seated right hemispheric infiltrating glioma, associated with a KIF5C::MET fusion. While histopathologic differential diagnosis favored infantile hemispheric glioma and pediatric diffuse high-grade glioma (H3, and IDH1 wildtype), DNA methylation profiling was suggestive of a lesion in the vicinity of low-grade glial/glial neuroepithelial tumor with a score of 0.725 for pilocytic astrocytoma and 0.753 for low-grade glial/ganglioneuro-epithelial tumor. The patient was treated with weekly vinblastine, which was discontinued at 3 months due to progression. More intensive chemotherapy as per POG9233/9234 also led to further tumor progression. Considering the patient’s young age and MET fusion, Crizotinib was accessed on a compassionate basis. Three months into therapy, tumor size decreased by 10%. At six months of treatment, there was significant improvement of her left hemiparesis and MRI evaluation demonstrated an 80% decrease in tumor size. Crizotinib is well-tolerated except for uncomplicated grade 3 neutropenia. We report the first case of pediatric glioma successfully treated with crizotinib. This illustrates the importance of integrated molecular diagnosis and documents effectiveness of ALK inhibitor in MET fusion-driven pediatric gliomas.