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.
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.
Carson
Kenneth R
KR
Department of Internal Medicine, Division of Medical Oncology, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, USA.
Focosi
Daniele
D
Major
Eugene O
EO
Petrini
Mario
M
Richey
Elizabeth A
EA
West
Dennis P
DP
Bennett
Charles L
CL
D016907:Adverse Drug Reaction Reporting Systems; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000453:epidemiology; D000069442:Natalizumab; D000069283:Rituximab; D013601:T-Lymphocytes / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069442:Natalizumab; D000069283:Rituximab; C472181:efalizumab