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Ten years later, progressive multifocal leukoencephalopathy (PML), until that time a rare opportunistic infection mostly seen in AIDS patients, was added as a black box warning after retrospective case\u2010control studies showed an increased incidence in both B\u2010cell lymphoproliferative disorders and autoimmune diseases. Despite more than 5 million worldwide exposures to date (and about 500 000 new exposures per year), insufficient data collection has hampered identification of risk minimization strategies, and concerns have been raised about a class effect extending to the newer anti\u2010CD20 monoclonal antibodies (ofatumumab, obinutuzumab, and ocrelizumab). Here, we report current PML case counts registered in the FAERS and EudraVigilance databases and comment on severe CD4<jats:sup>+<\/jats:sup> T lymphopenia as a plausible common mechanism of action for anti\u2010CD20 antibodies in causation of PML.<\/jats:p>","DOI":"10.1002\/rmv.2077","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T13:04:40Z","timestamp":1564664680000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Progressive multifocal leukoencephalopathy and anti\u2010CD20 monoclonal antibodies: What do we know after 20 years of rituximab"],"prefix":"10.1002","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8811-195X","authenticated-orcid":false,"given":"Daniele","family":"Focosi","sequence":"first","affiliation":[{"name":"North\u2010Western Tuscany Blood Bank Pisa University Hospital  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Tuccori","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"},{"name":"Unit of Adverse Drug Reaction Monitoring Pisa University Hospital  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7489-5271","authenticated-orcid":false,"given":"Fabrizio","family":"Maggi","sequence":"additional","affiliation":[{"name":"Department of Translational Research University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.4.1486"},{"key":"e_1_2_15_3_1","unstructured":"Rituximab (marketed as Rituxan): progressive multifocal leukoencephalopathy (PML).http:\/\/www.fda.gov\/Drugs\/DrugSafety\/DrugSafetyNewsletter\/ucm115974.htm[December 31 2017]."},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2016.1198775"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ1220"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-017-0536-x"},{"key":"e_1_2_15_7_1","first-page":"216","article-title":"Is there a (host) genetic predisposition to progressive multifocal leukoencephalopathy?","volume":"6","author":"Hatchwell E","year":"2015","journal-title":"FrontImmunol"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.279"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20431"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21619"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24192"},{"key":"e_1_2_15_12_1","unstructured":"List of licensed biological products with (1) Reference Product Exclusivity and (2) Biosimilarity or Interchangeability Evaluation to Date.https:\/\/www.fda.gov\/downloads\/Drugs\/DevelopmentApprovalProcess\/HowDrugsareDevelopedandApproved\/ApprovalApplications\/TherapeuticBiologicApplications\/Biosimilars\/UCM560162.pdf[November 24 2017]."},{"key":"e_1_2_15_13_1","unstructured":"European public assessment reports\u2014Biosimilars.http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages%2Fmedicines%2Flanding%2Fepar_search.jsp&mid=WC0b01ac058001d124&searchTab=searchByAuthType&alreadyLoaded=true&isNewQuery=true&status=Authorised&keyword=Enter+keywords&searchType=name&taxonomyPath=&treeNumber=&searchGenericType=biosimilars&genericsKeywordSearch=Submit[November 24 2017]."},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-186999"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp256"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2010-0098"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2014.32.15_suppl.e19540"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2015.33.15_suppl.e18033"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051782"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051847"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051586"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70161-5"},{"key":"e_1_2_15_23_1","unstructured":"EMA: Assessment report for the post\u2010authorisation measure LEG096dated 9 October2017."},{"key":"e_1_2_15_24_1","first-page":"106","article-title":"Immunochemotherapy with bendamustine\u2010rituximab (BR) as induction therapy for indolent lymphomas results in a severe lymphopenia with low CD4+ and CD8+ counts without an increase in atypical infections. 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