Progressive multifocal leukoencephalopathy and anti‐CD20 monoclonal antibodies: What do we know after 20 years of rituximab

Summary In 1997, rituximab was the first monoclonal antibody clinically approved for the treatment of cancer. 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 retrosp...

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Bibliographic Details
Published in:Reviews in medical virology 2019-11, Vol.29 (6), p.e2077-n/a
Main Authors: Focosi, Daniele, Tuccori, Marco, Maggi, Fabrizio
Format: Article
Language:English
Subjects:
Antibody-Dependent Cell Cytotoxicity - immunology
Antineoplastic Agents, Immunological - adverse effects
Antineoplastic Agents, Immunological - therapeutic use
Apoptosis - immunology
Autoimmune diseases
CD20
CD20 antigen
CD4 antigen
Complement System Proteins - immunology
Data collection
Encephalitis
Exposure
Humans
Immunoglobulins
Immunoproliferative diseases
Immunotherapy
Incidence
JC virus
JC Virus - physiology
Leukoencephalopathy
Leukoencephalopathy, Progressive Multifocal - epidemiology
Leukoencephalopathy, Progressive Multifocal - etiology
Leukoencephalopathy, Progressive Multifocal - metabolism
Lymphocytes
Lymphopenia
Lymphopenia - blood
Lymphopenia - complications
Monoclonal antibodies
obinutuzumab
ofatumumab
Opportunist infection
Phagocytosis - immunology
Polyomavirus Infections - complications
Polyomavirus Infections - virology
Progressive multifocal leukoencephalopathy
Public Health Surveillance
Risk Assessment
Risk Factors
Rituximab
Rituximab - adverse effects
Rituximab - therapeutic use
Targeted cancer therapy
Viral infections
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Summary:Summary In 1997, rituximab was the first monoclonal antibody clinically approved for the treatment of cancer. 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‐control studies showed an increased incidence in both B‐cell 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‐CD20 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+ T lymphopenia as a plausible common mechanism of action for anti‐CD20 antibodies in causation of PML.
ISSN:1052-9276
1099-1654
DOI:10.1002/rmv.2077