Glioblastoma in natalizumab‐treated multiple sclerosis patients

Morales, Fabian Sierra; Wright, Robert B.; Novo, Jorge; Arvanitis, Leonidas; Stefoski, Dusan; Koralnik, Igor J.

doi:10.1002/acn3.428

Cited by 10 publications

(7 citation statements)

References 24 publications

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“…We found three published reports of MS and glioma co-occurrence in patients on fingolimod, 37-39 one on dimethyl fumarate, 40 and two on natalizumab. 41 There were also twelve cases of co-occurrence on fingolimod reported to the Belgium center for pharmacovigilance. 37 Fingolimod has been found to have strong in vitro anti-tumor activity; on the other hand, fingolimod causes downstream activation of p21-activated kinase 1 (Pak1), the increased activation of which in neoplastic glial cells has been correlated with shorter survival time in GBM patients.…”

Section: Discussionmentioning

confidence: 99%

Glioblastoma in Patients With Multiple Sclerosis

Berkman

Nakhate

Castro

2022

The Neurohospitalist

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Background Although rare, the co-occurrence of multiple sclerosis (MS) and glioma poses unique challenges in terms of diagnosis and management for both neurologists and neuro-oncologists. Methods Here we report on a single-center cohort of four patients with a diagnosis of multiple sclerosis who developed gliomas. Results Our cohort reflects the epidemiology of glioma in terms of the relative frequency of IDH-wildtype and IDH-mutant cases. The patients in 3 out of the 4 cases presented did not develop their tumors in areas of pre-existing demyelinating lesions. Conclusions We did not find evidence to support the hypothesis that chronic gliosis from demyelinating plaques may serve as a substrate for secondary induction of a glial neoplasm. In our Discussion, we provide recommendations for distinguishing neoplastic from demyelinating lesions, review the evidence for demyelination as a risk factor for gliomagenesis, and highlight important considerations for the concurrent management of glioma and MS.

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Section: Discussionmentioning

confidence: 99%

Glioblastoma in Patients With Multiple Sclerosis

Berkman

Nakhate

Castro

2022

The Neurohospitalist

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“…1,2 DLBCL constitutes approximately 30% of all lymphomas, with the upper gastrointestinal tract (GIT) being the most common site of extranodal presentation, with an incidence of 0.5 cases/ 100,000 person years. 3 After a single report of natalizumab-associated gastric DLBCL in a 61year-old male patient with MS, we report a further 2 cases of gastric DLBCL from a single center.…”

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confidence: 90%

“…Despite good tolerability and safety, natalizumab is associated with hepatotoxicity, PML, cutaneous zoster, and, rarely, melanomas and gliomas. 1–3 Individual case reports have suggested a link with hematological neoplasia's including primary CNS lymphoma (PCNSL), peripheral T-cell lymphoma (PTCL), and extranodal diffuse large B-cell lymphoma (DLBCL). 1,2…”

mentioning

confidence: 99%

“…Despite good tolerability and safety, natalizumab is associated with hepatotoxicity, PML, cutaneous zoster, and, rarely, melanomas and gliomas. [1][2][3] Individual case reports have suggested a link with hematological neoplasia's including primary CNS lymphoma (PCNSL), peripheral T-cell lymphoma (PTCL), and extranodal diffuse large B-cell lymphoma (DLBCL). 1,2 DLBCL constitutes approximately 30% of all lymphomas, with the upper gastrointestinal tract (GIT) being the most common site of extranodal presentation, with an incidence of 0.5 cases/ 100,000 person years.…”

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confidence: 99%

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Upper Gastrointestinal Tract Lymphoma With Natalizumab

et al. 2021

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The humanised recombinant monoclonal antibody natalizumab (Tysabri), is a selective antagonist of the α4 subunit of the leukocyte adhesion molecule integrin, VLA-3. Blockade of VLA-3 leads to inhibition of immune cell transmigration into target organs, notably the intestinal lining and central nervous system.1,2 Natalizumab is approved to treat relapsing-remitting Multiple Sclerosis (RRMS) in the US and Europe, and Crohn’s Disease in the US. Following approval in 2004, natalizumab was withdrawn in 2005 due to 3 reported cases of progressive multifocal leukoencephalopathy (PML). In 2006, it re-entered the market with additional monitoring requirements.

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“…As immune surveillance is critical in cancer development, a possible causal “immuno-genetic” relationship between neuroinflammatory diseases and malignant brain tumors has been repeatedly discussed 3 . Proposed cancer-promoting mechanisms include a malignant transformation of multiple sclerosis plaques 4 and immunosuppression induced by immunomodulatory therapies 5 6 7 . However, two population-based studies could not verify an altered risk for gliomas in patients with MS 8 9 .…”

Section: Introductionmentioning

confidence: 99%

Concurrent gliomas in patients with multiple sclerosis

Sahm

Keßler

Eisele

et al. 2022

Preprint

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Concurrent malignant brain tumors in patients with multiple sclerosis (MS) constitute a rare but paradigmatic phenomenon for studying neuroimmunological mechanisms from both molecular and clinical perspectives. A multicenter cohort of 26 patients diagnosed with both primary brain tumors and multiple sclerosis was studied for disease localization, tumor treatment-related MS activity, and molecular characteristics specific for diffuse glioma in MS patients. MS neither predisposes nor protects from the development of gliomas. Patients with glioblastoma WHO grade IV without IDH mutations had a longstanding history of MS, whereas patients diagnosed with IDH-mutant astrocytoma WHO grade II received multiple sclerosis diagnosis mostly at the same time or later. Concurrent MS was associated with a lesser extent of tumor resection and a worse prognosis in IDH-mutant glioma patients (PFS 32 vs. 64 months, p=0.0206). When assessing tumor-intrinsic differences no distinct subgroup-defining methylation pattern was identified in gliomas of MS patients compared to other glioma samples. However, differential methylation of immune-related genetic loci including human leukocyte antigen locus on 6p21 and interleukin locus on 5q31 was found in MS patients vs. matched non-MS patients. In line, inflammatory disease activity increased in 42% of multiple sclerosis patients after brain tumor radiotherapy suggesting a susceptibility of multiple sclerosis brain tissue to pro-inflammatory stimuli such as ionizing radiation. Concurrent low-grade gliomas should be considered in multiple sclerosis patients with slowly progressive, expansive T2/FLAIR lesions. Our findings of typically reduced extent of resection in MS patients and increased MS activity after radiation inform future treatment decisions.

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Glioblastoma in natalizumab‐treated multiple sclerosis patients

Cited by 10 publications

References 24 publications

Glioblastoma in Patients With Multiple Sclerosis

Glioblastoma in Patients With Multiple Sclerosis

Upper Gastrointestinal Tract Lymphoma With Natalizumab

Concurrent gliomas in patients with multiple sclerosis

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