P20.05.A USE OF VISMODEGIB IN ADULT PATIENTS WITH NEOPLASTIC MENINGITIS FROM SONIC HEDGEHOG (SHH)-ACTIVATED MEDULLOBLASTOMAS: A CASE REPORT

Abstract

Abstract BACKGROUND Vismodegib is a SHH-inhibitor that proved to be effective in locally-recurrent SHH-activated medulloblastoma. However, whether vismodegib is effective in case of neoplastic meningitis (NM) as well has not been assessed so far. Here, we present a case of a patient with NM from SHH-activated medulloblastoma who showed a dramatic response to vismodegib. Case Report: A 34-year-old patient was diagnosed with a SHH-activated cerebellar medulloblastoma in 2015. He underwent gross-total resection, cranio-spinal radiotherapy (RT) and 5 cycles of lomustine, vincristine and cisplatin. Then, he remained disease-free until October 2021, when the MRI showed a new single contrast-enhanced nodule in the spine (T10), which was treated with stereotactic RT. However, the following MRI showed a diffuse leptomeningeal involvement, with new multiple linear and nodular lesions. The CSF cytology confirmed the presence of neoplastic cells. Therefore, in April 2022 vismodegib (150 mg daily) was started. The treatment was well tolerated, except for increased creatine phosphokinase (CTCAE v3.0 grade 1). After only 2 months of therapy, a reduction of the meningeal enhancement was seen on MRI, and after 4 months all nodular and linear lesions disappeared. Similarly, CSF cytology became negative after 4 months of treatment. However, after 8 months of treatment (December 2022), the MRI of the spine showed the new appearance of meningeal contrast-enhanced lesions, and CSF cytology confirmed the presence of neoplastic cells. Therefore, vismodegib was dismissed. In few days, the patient (who did not have any symptoms so far) developed severe meningeal symptoms, and palliative care was started, until his death in February 2023. CONCLUSION To our knowledge, this is the first report of an adult patient with NM from SHH-activated medulloblastoma achieving a complete response with vismodegib, even if temporary. Data from larger series are needed to confirm the effectiveness and safety of vismodegib in case of leptomeningeal spread.