ArticleBMC cancer2019
Intracranial antitumor responses of nivolumab and ipilimumab: a pharmacodynamic and pharmacokinetic perspective, a scoping systematic review.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Intrathecal immune checkpoint inhibitors as adjunctive therapy for leptomeningeal disease: A case series and systematic review.Neurosurgical review · 2026Pooled it
- Mixed Response to Nivolumab Among Different Metastatic Sites in Patients With Metastatic Renal Cell Carcinoma: Incidence and Clinical Implications.International journal of urology : official journal of the Japanese Urological Association · 2026Article
- Biologic immunomodulators and spinal fusion: evidence, mechanisms, and perioperative considerations.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- PD-1 Blockade-Induced DKK1 Expression by CD8+ T Cells Promotes Blood-Brain Barrier Permeabilization.Cancer discovery · 2026Article
- Immunotherapy combined with cranial radiotherapy for driver-negative non-small-cell lung cancer brain metastases: a retrospective study.Future oncology (London, England) · 2026Article
- Brain neurovascular unit in response to intra- and extra-central nervous system cancers: implications, mechanisms, and challenges.Cancer cell international · 2025Review
- Dramatic Inflammatory Regression of Choroidal Metastases from Renal Cell Carcinoma following Ipilimumab and Nivolumab Immunotherapy: A Case Series.Ocular oncology and pathology · 2025Article
- Immune checkpoint inhibition perturbs neuro-immune homeostasis and impairs cognitive function.Journal of experimental & clinical cancer research : CR · 2025Article
- Prognostic impact of biomarkers in PMBCL: rationale for early integration of immune checkpoint inhibitors.Exploration of targeted anti-tumor therapy · 2025Article
- Advances in primary large B-cell lymphoma of immune-privileged sites.Frontiers in immunology · 2025Review
- Immunotherapy against glioblastoma using backpack-activated neutrophils.Bioengineering & translational medicine · 2025Article
- Intracranial administration of anti-PD-1 and anti-CTLA-4 immune checkpoint-blocking monoclonal antibodies in patients with recurrent high-grade glioma.Neuro-oncology · 2024Article
- Immunomodulatory signalling networks in glioblastoma multiforme: a comprehensive review of therapeutic approaches.Human cell · 2024Review
- Real-world evaluation of first-line treatment of extensive-stage small-cell lung cancer with atezolizumab plus platinum/etoposide: a focus on patients with brain metastasis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Distribution of Bevacizumab into the Cerebrospinal Fluid of Children and Adolescents with Recurrent Brain Tumors.Paediatric drugs · 2024Article
- A case report and literature review on primary intracranial malignant melanoma: Challenges and insights.International journal of surgery case reports · 2024Article
- Case report: Concurrent intrathecal and intravenous pembrolizumab for metastatic melanoma with leptomeningeal disease.Frontiers in oncology · 2024Article
- Article
- Enhanced brain entry of checkpoint-inhibitory therapeutic antibodies facilitated by intraarterial NEO100 in mouse models of brain-localized malignancies.Journal of neurosurgery · 2023Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecently, two phase II trials showed intracranial activity of the immune checkpoint inhibitors nivolumab and ipilimumab in patients with melanoma brain metastases. However, it is generally assumed that large molecules like monoclonal antibodies nivolumab and ipilimumab cannot penetrate and pass an intact blood brain barrier (BBB). In this systematic review we provide a pharmacodynamic and pharmacokinetic consideration of the clinical activity of the immune checkpoint inhibitors nivolumab and ipilimumab in melanoma brain metastases.
methodsPubmed was systematically searched for prospective phase II and III studies on nivolumab and ipilimumab in melanoma brain metastases and cerebrospinal fluid (CSF) levels of nivolumab and ipilimumab. Results were discussed and a perspective on the pharmacodynamics and pharmacokinetics for the intracranial activity of these agents was given.
resultsTwo phase II studies with the combination nivolumab and ipilimumab and one phase II study with ipilimumab monotherapy in melanoma brain metastases were included in this review. One article reported drug levels of nivolumab in CSF. Intracranial responses were achieved in 16 of 35 patients (46%; 95% confidence interval (CI) 29-63) in a phase II study cohort treated with nivolumab and ipilimumab. In a second phase II study in 94 patients, the rate of intracranial clinical benefit was 57% (95% CI 47-68). The CSF/serum ratio of nivolumab was 0.88-1.9% in a cohort of metastatic melanoma patients treated with nivolumab 1-3 mg/kg. Nivolumab concentrations ranged from 35 to 150 ng/ml in CSF of these patients, which is in the range of the half maximal effective concentration (EC50) of 0.64 nM.
conclusionsIpilimumab and nivolumab are active in melanoma brain metastases. Nivolumab penetrates into the CSF. Based on the described findings the general consensus that monoclonal antibodies do not penetrate into the central nervous system (CNS) and cannot have a direct intracranial effect needs to be reconsidered.
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