Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a Review from the Research on Adverse Drug Events and Reports (RADAR) Project

Kenneth R. Carson, Daniele Focosi, Eugene O. Major, Mario Petrini, Elizabeth A. Richey, Dennis P. West, Charles L. Bennett*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

375 Scopus citations

Abstract

Progressive multifocal leucoencephalopathy (PML) is a serious and usually fatal CNS infection caused by JC polyoma virus. CD4+ and CD8+ T lymphopenia, resulting from HIV infection, chemotherapy, or immunosuppressive therapy, are the primary risk factors. The immune modulatory monoclonal antibodies rituximab, natalizumab, and efalizumab have received regulatory approval in the USA and Europe for treatment of non-Hodgkin lymphoma, rheumatoid arthritis, and chronic lymphocytic leukaemia (Europe only); multiple sclerosis and Crohn's disease; and psoriasis, respectively. Efalizumab and natalizumab administration is associated with CD4+ T lymphopenia and altered trafficking of T lymphocytes into the CNS, and rituximab leads to prolonged B-lymphocyte depletion. Unexpected cases of PML developing in people who receive these drugs have been reported, with many of the affected individuals dying from this disease. Herein, we review clinical findings, pathology, epidemiology, basic science, and risk-management issues associated with PML infection developing after treatment with these monoclonal antibodies.

Original languageEnglish (US)
Pages (from-to)816-824
Number of pages9
JournalThe Lancet Oncology
Volume10
Issue number8
DOIs
StatePublished - Aug 1 2009

ASJC Scopus subject areas

  • Oncology

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