{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T05:33:07Z","timestamp":1792474387069,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Our aim was to assess the real\u2010world effectiveness of immune checkpoint inhibitors for treatment of patients with progressive multifocal leukoencephalopathy (PML).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add\u2010on to standard of care. One\u2010year follow\u2010up data were analyzed to determine clinical outcomes and safety profile. Logistic regression was used to identify variables associated with 1\u2010year survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Predisposing conditions included hematological malignancy (n\u00a0=\u00a038, 48.1%), primary immunodeficiency (n\u00a0=\u00a014, 17.7%), human immunodeficiency virus\/acquired immunodeficiency syndrome (n\u00a0=\u00a012, 15.2%), inflammatory disease (n\u00a0=\u00a08, 10.1%), neoplasm (n\u00a0=\u00a05, 6.3%), and transplantation (n\u00a0=\u00a02, 2.5%). Pembrolizumab was most commonly used (n\u00a0=\u00a053, 67.1%). One\u2010year survival was 51.9% (41\/79). PML\u2013immune reconstitution inflammatory syndrome (IRIS) was reported in 15 of 79 patients (19%). Pretreatment expression of programmed cell death\u20101 on circulating T cells did not differ between survivors and nonsurvivors. Development of contrast enhancement on follow\u2010up magnetic resonance imaging at least once during follow\u2010up (OR\u00a0=\u00a03.16, 95% confidence interval\u00a0=\u00a01.20\u20138.72,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u20090.02) was associated with 1\u2010year survival. Cerebrospinal fluid JC polyomavirus DNA load decreased significantly by 1\u2010month follow\u2010up in survivors compared to nonsurvivors (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u20090.0001). Thirty\u2010two adverse events occurred among 24 of 79 patients (30.4%), and led to treatment discontinuation in 7 of 24 patients (29.1%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>In this noncontrolled retrospective study of patients with PML who were treated with immune checkpoint inhibitors, mortality remains high. Development of inflammatory features or overt PML\u2010IRIS was commonly observed. This study highlights that use of immune checkpoint inhibitors should be strictly personalized toward characteristics of the individual PML patient. ANN NEUROL 2023;93:257\u2013270<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26512","type":"journal-article","created":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T04:24:25Z","timestamp":1663993465000},"page":"257-270","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7618-3585","authenticated-orcid":false,"given":"Xavier","family":"Boumaza","sequence":"first","affiliation":[{"name":"Department of Infectious and Tropical Diseases Toulouse University Hospital  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Bonneau","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, CIC 1436 Toulouse University Hospital  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Roos\u2010Weil","sequence":"additional","affiliation":[{"name":"Department of Hematology Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Pinnetti","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Clinical Unit National Institute for Infectious Disease \"L. Spallanzani\"  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Rauer","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical Center, University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa","family":"Nitsch","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Del Bello","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Organ Transplantation CHU Rangueil  Toulouse France"},{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291, CNRS UMR5051, Toulouse III University  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilijas","family":"Jelcic","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology University Hospital Zurich and University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt\u2010Wolfram","family":"S\u00fchs","sequence":"additional","affiliation":[{"name":"Clinical Neuroimmunology and Neurochemistry, Department of Neurology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Gasnault","sequence":"additional","affiliation":[{"name":"Unit of Rehabilitation of Neuroviral Diseases Bic\u00eatre Hospital, APHP  Le Kremlin\u2010Bic\u00eatre France"},{"name":"INSERM U1186 Paul Brousse Hospital, Paris Saclay University  Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin","family":"Goreci","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Grauer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Translational Neurology University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharmilee","family":"Gnanapavan","sequence":"additional","affiliation":[{"name":"Department of Neurology Barts Health NHS Trust and Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6661-6081","authenticated-orcid":false,"given":"Rebecca","family":"Wicklein","sequence":"additional","affiliation":[{"name":"Department of Neurology Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6660-0100","authenticated-orcid":false,"given":"Nicolas","family":"Lambert","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital of Li\u00e8ge  Li\u00e8ge Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Perpoint","sequence":"additional","affiliation":[{"name":"Department of Infectious and Tropical Diseases Lyon University Hospital  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"Beudel","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Center University of Amsterdam  Amsterdam the Netherlands"},{"name":"Department of Neuroscience Amsterdam University Medical Center  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Clifford","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University in St Louis  St Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Sommet","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, CIC 1436 Toulouse University Hospital  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Cortese","sequence":"additional","affiliation":[{"name":"Experimental Immunotherapeutics Unit National Institute of Neurological Disorders and Stroke  Bethesda MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8363-7028","authenticated-orcid":false,"given":"Guillaume","family":"Martin\u2010Blondel","sequence":"additional","affiliation":[{"name":"Department of Infectious and Tropical Diseases Toulouse University Hospital  Toulouse France"},{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291, CNRS UMR5051, Toulouse III University  Toulouse France"},{"name":"European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Infections of the Brain (ESGIB)  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Immunotherapy for PML Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00427-y"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26307"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00174-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1815039"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1816198"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1514296"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00207"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0221-9"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix191"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.112"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq365"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828c2fa1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1474523"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22408"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ1220"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020967"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181c0d4a1"},{"key":"e_1_2_9_19_1","unstructured":"Medical information. TYSABRI (natalizumab): PML incidence in patients receiving natalizumab.Cambridge MA: Biogen 2022."},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac237"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr206"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000194804.97164.86"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh215"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200307040-00004"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01809-06"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440309"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a43e6d"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0900-5"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70026-8"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12963"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1086\/427698"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1086\/315817"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/313598"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26198"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10952-5"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr1404664"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04444"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07662"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1972"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003856"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz374"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520942201"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31825a313c"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064313"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19330"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.07.021"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2020.02.005"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02506-10"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318268465b"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000001097"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000343510.08643.74"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.26512","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ana.26512","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.26512","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T00:36:47Z","timestamp":1692319007000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.26512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,17]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1002\/ana.26512"],"URL":"https:\/\/doi.org\/10.1002\/ana.26512","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,17]]},"assertion":[{"value":"2022-04-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}