Exceptional response of radiotherapy-naïve cranial meningiomas to dual immune checkpoint blockade in BAP1 tumor predisposition syndrome.

Meningiomas are the most common primary central nervous system tumors, and while most are benign, atypical and anaplastic variants frequently recur and have limited effective treatment options. Recent trials of PD-1 blockade in unselected meningioma cohorts have demonstrated modest activity, with low objective response rates. These findings highlight the need to identify molecular biomarkers that may predict immunotherapy sensitivity in this disease. BRCA1-associated protein 1 (BAP1) is a tumor suppressor critical for chromatin regulation and DNA repair, and germline pathogenic variants cause BAP1 tumor predisposition syndrome (BAP1-TPDS), a hereditary cancer syndrome characterized by uveal melanoma, mesothelioma, renal cell carcinoma, meningioma, among other tumors. In sporadic meningiomas, BAP1 alterations are rare but define an aggressive molecular subset with poor outcomes. Here, we describe a patient with BAP1-TPDS and multifocal cranial meningiomas who experienced exceptional radiographic regression of her tumors while receiving dual immune checkpoint blockade for metastatic uveal melanoma.