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

Our plain-English summary of Exceptional response of radiotherapy-naïve cranial meningiomas to dual immune checkpoint blockade in BAP1 tumor predisposition syndrome, by G.L. Gallia, C.L. Hann, C.G. Lucas, et al (Neuro-oncology Advances, 2026).

The study

• Authors: G.L. Gallia, C.L. Hann, C.G. Lucas, L.P. Luna, D.O. Kamson, T. Sato
• Journal: Neuro-oncology Advances
• Published: 2026;8(1):vdag095
• Read it: PubMed · Publisher · Free full text

Abstract

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.

© The Author(s) 2026. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

In plain English

This was a case report about one woman with BAP1 tumor predisposition syndrome, an inherited condition. It did not concern asbestos exposure. She was first seen at the authors' institution in 2020, aged 60, with multiple meningiomas (brain-lining tumors). These had been operated on five times; the 2022 specimen was graded atypical (WHO grade 2) with BAP1 loss. The meningiomas had never received radiotherapy, though she had plaque radiotherapy for a left-eye melanoma. Germline testing found a likely pathogenic BAP1 variant. After metastatic uveal melanoma was diagnosed in 2024, she started ipilimumab plus nivolumab. Her intradural meningiomas first enlarged and then shrank, while a sinonasal/skull base meningioma shrank without first enlarging; none received local treatment. At 16 months, two-dimensional measurements had fallen 67% and tumor volume 80%, meeting criteria for a partial response. That specimen's tumor mutation burden was 0.00 mutations/megabase; a melanoma metastasis measured 1.76. The authors concluded that BAP1 status may be a candidate marker of immunotherapy sensitivity in meningioma. They noted that one case cannot establish cause and that her melanoma treatment and anastrozole were possible confounders.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-patient case report (Molecular Tumor Board Case Report)
• Who was studied: One 60-year-old woman seen at the authors' institution (Johns Hopkins) from 2020. She had BAP1 tumor predisposition syndrome and multiple cranial meningiomas, and later developed metastatic uveal melanoma.
• Exposure: No asbestos exposure is discussed. The exposure studied was dual immune checkpoint blockade, given for metastatic uveal melanoma: four induction cycles of ipilimumab and nivolumab, followed by maintenance nivolumab every 4 weeks.
• Main results:
  • The patient's meningiomas were operated on five times, most recently in 2022
  • The 2022 meningioma specimen was an atypical meningioma (WHO grade 2) with loss of BAP1 expression in most tumor cells
  • Germline testing found a likely pathogenic splice donor variant in BAP1, consistent with BAP1 tumor predisposition syndrome
  • The tumor mutation burden of the 2022 meningioma specimen was 0.00 mutations/megabase
  • The tumor mutation burden of the biopsied metastatic uveal melanoma (tibial nodule, sequenced in 2024) was 1.76 mutations/megabase
  • Tumor mutation burden and immune characterization of the meningiomas came from a single pre-treatment meningioma specimen
  • The patient's meningiomas had not received intracranial radiotherapy. She had earlier received plaque radiotherapy for a ciliochoroidal melanoma of the left eye in 2011.
  • Plaque radiotherapy was given for the 2011 left-eye melanoma
  • Metastatic uveal melanoma was diagnosed by biopsy in early 2024
  • After four cycles of treatment, the right parietal meningioma showed interval enlargement, and her other intradural tumors also enlarged
  • An MRI taken 7 months after starting immunotherapy showed a marked reduction in the right parietal lesion and in the smaller meningiomas, and surgery was deferred
  • At 16 months after starting immunotherapy, the patient had a 67% reduction in bidimensional measurements, consistent with a partial response by RANO criteria
  • Volumetric analysis showed an 80% decrease in tumor volume compared with the pre-treatment scan
  • A sinonasal/skull base meningioma also shrank, without an initial increase in size
  • No local therapy was given to any of the shrinking tumor sites
  • The authors judged the early enlargement compatible with immune-related pseudoprogression, but said this cannot be definitively established
  • Staining of the pre-treatment tumor showed abundant macrophage-type (CD68- and CD163-positive) cells and relatively few T cells
• The authors' conclusion: The authors concluded that this case raises the possibility that BAP1 status may be a candidate biomarker of immunotherapy sensitivity in meningioma, and that molecularly defined subgroups need systematic investigation
• Limitations the authors state:
  • As a single observation, the report cannot establish causality between BAP1 loss and immunotherapy responsiveness
  • Concurrent treatment for metastatic uveal melanoma is a potential confounding variable
  • Anastrozole taken for breast cancer during the same period is another potential confounder
  • Immune characterization and tumor mutation burden came from a single pre-treatment meningioma specimen
  • No MRI was obtained at the start of immunotherapy

Topics

Medical terms in this study, explained in our Lexicon: BAP1 Tumor Predisposition Syndrome, Biomarker, Immunotherapy, BAP1, Mesothelioma, Carcinoma.

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