Trial reportThe New England journal of medicine2019
Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy.
Abstract readClinical Trial
In one paragraph
Trial report in The New England journal of medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
187citing papers in PubMed, 1 pooled it
25.0field-weighted citation impact, top 1% of its field
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
187 citing papers in PubMed, 1 synthesis or guideline pooled it, 352 citations in OpenAlex.
- The Association Between the Incidence Risk of Peripheral Neuropathy and PD-1/PD-L1 Inhibitors in the Treatment for Solid Tumor Patients: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2019Pooled it
- Tenofovir in Progressive Multifocal Leukoencephalopathy: Virus Suppression Without Clinical Benefit in 2 Cases.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- The use of pembrolizumab in a patient with progressive multifocal leukoencephalopathy associated with Good's syndrome: a case report.Acta neurologica Belgica · 2026Article
- Safety, Immunovirologic, and Central Nervous System Effects of PD-1 Inhibition in People With HIV Without Malignancy.The Journal of infectious diseases · 2026Article
- Bispecific Antibodies Are Associated With Progressive Multifocal Leukoencephalopathy.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Pembrolizumab in people with HIV-associated progressive multifocal leukoencephalopathy: a retrospective case series.Infection · 2026Article
- PD-1 regulates CD4Nature communications · 2026Article
- Guideline of the German Society of Neurology (DGN): "diagnosis and therapy of HIV-1-associated neurological disorders".Neurological research and practice · 2026Review
- Characteristics of progressive multifocal leukoencephalopathy in hematological malignancies, With reference to HIV-infected patients.International journal of hematology · 2026Article
- Current Perspectives on JC Polyomavirus Transmission and Associated Diseases: Implications for Prevention in Risk Populations.Viruses · 2026Review
- Genetic mechanisms underlying host susceptibility to central nervous system viral infections.Current opinion in infectious diseases · 2026Review
- Outcome Predictors in Progressive Multifocal Leukoencephalopathy Associated With Multiple Sclerosis Treatments: A Multicenter Cohort Study.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Pembrolizumab-Responsive Cerebellar PML in Untreated Sarcoidosis: A Case Report.Cerebellum (London, England) · 2026Article
- Adoptive T-cell therapy for virus-associated diseases.Clinical microbiology reviews · 2025Review
- Overview of MRI findings in progressive multifocal leukoencephalopathy.Japanese journal of radiology · 2025Review
- Reduced incidence of relapse after checkpoint inhibitors relative to brentuximab vedotin as salvage therapy before allogeneic stem cell transplantation for refractory/relapsed Hodgkin lymphoma: A retrospective analysis.British journal of haematology · 2025Article
- Successful treatment of HIV-related progressive multifocal leukoencephalopathy and immunological reconstitution inflammatory syndrome with intravenous human immunoglobulin: a case report.AIDS research and therapy · 2025Article
- Progressive Multifocal Leukoencephalopathy (PML) after hematopoietic cell transplantation (HCT): a retrospective study of Infectious Diseases Working Party (IDWP) of the EBMT.Bone marrow transplantation · 2025Article
- Donor Variability and PD-1 Expression Limit BK Polyomavirus-specific T-cell Function and Therapy.Transplantation · 2025Article
- A Case Report of Progressive Multifocal Leukoencephalopathy (PML) in an Immunocompetent Patient.Cureus · 2025Article
127 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Irene CorteseFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
Pawel MuranskiFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
Yoshimi Enose-AkahataFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
Seung-Kwon HaFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
Bryan SmithFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
MariaChiara MonacoFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
Caroline RyschkewitschFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
Eugene O MajorFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
Joan OhayonFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
Matthew K SchindlerFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
Erin BeckFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
Lauren B ReomaFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
Steve JacobsonFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
Daniel S ReichFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).ORCID 0000-0002-2628-4334
Avindra NathFrom the Neuroimmunology Clinic (I.C., J.O.), the Viral Immunology Section (Y.E.-A., S.J.), the Section of Infections of the Nervous System (B.S., L.B.R., A.N.), the Laboratory of Molecular Medicine and Neuroscience (M.M., C.R., E.O.M.), and the Translational Neuroradiology Section (S.-K.H., M.K.S., E.B., D.S.R.), National Institute of Neurological Disorders and Stroke, and the Hematology Branch, National Heart, Lung, and Blood Institute (P.M.), National Institutes of Health, Bethesda, MD; and the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York (P.M.).
National Institute of Neurological Disorders and Stroke · USLaboratory of Molecular Genetics · PLThe Neurological Institute · USGlobal Viral · USInstitute of Neuroimmunology of the Slovak Academy of Sciences · SKNational Institutes of Health · US
Funding
Multimodal MRI in Multiple SclerosisZIANS003119 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI REICH, DANIEL · 2010 to 2025
$53.4MAbstract
backgroundProgressive multifocal leukoencephalopathy (PML) is an opportunistic brain infection that is caused by the JC virus and is typically fatal unless immune function can be restored. Programmed cell death protein 1 (PD-1) is a negative regulator of the immune response that may contribute to impaired viral clearance. Whether PD-1 blockade with pembrolizumab could reinvigorate anti-JC virus immune activity in patients with PML was unknown.
methodsWe administered pembrolizumab at a dose of 2 mg per kilogram of body weight every 4 to 6 weeks to eight adults with PML, each with a different underlying predisposing condition. Each patient received at least one dose but no more than three doses.
resultsPembrolizumab induced down-regulation of PD-1 expression on lymphocytes in peripheral blood and in cerebrospinal fluid (CSF) in all eight patients. Five patients had clinical improvement or stabilization of PML accompanied by a reduction in the JC viral load in the CSF and an increase in in vitro CD4+ and CD8+ anti-JC virus activity. In the other three patients, no meaningful change was observed in the viral load or in the magnitude of antiviral cellular immune response, and there was no clinical improvement.
conclusionsOur findings are consistent with the hypothesis that in some patients with PML, pembrolizumab reduces JC viral load and increases CD4+ and CD8+ activity against the JC virus; clinical improvement or stabilization occurred in five of the eight patients who received pembrolizumab. Further study of immune checkpoint inhibitors in the treatment of PML is warranted. (Funded by the National Institutes of Health.).
Indexed as
AdultAgedAntibodies, Monoclonal, HumanizedBrainCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCerebrospinal FluidDown-RegulationFemaleHumansImmune Reconstitution Inflammatory SyndromeImmunologic FactorsJC VirusLeukoencephalopathy, Progressive MultifocalLymphocyte CountMagnetic Resonance ImagingAntibodies, Monoclonal, HumanizedImmunologic FactorsPDCD1 protein, humanpembrolizumabProgrammed Cell Death 1 Receptor
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