Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Nov;29(6):e2077.
doi: 10.1002/rmv.2077. Epub 2019 Aug 1.

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

Daniele Focosi  1 , Marco Tuccori  2   3 , Fabrizio Maggi  4
Affiliations
Review

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

Daniele Focosi et al. Rev Med Virol. 2019 Nov.

Abstract

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.

Keywords: CD20; JC virus; obinutuzumab; ofatumumab; progressive multifocal leukoencephalopathy; rituximab.

PubMed Disclaimer

References

REFERENCES

    1. Goldberg SL, Pecora AL, Alter RS, et al. Unusual viral infections (progressive multifocal leukoencephalopathy and cytomegalovirus disease) after high-dose chemotherapy with autologous blood stem cell rescue and peritransplantation rituximab. Blood. 2002;99(4):1486-1488.
    1. Rituximab (marketed as Rituxan): progressive multifocal leukoencephalopathy (PML). http://www.fda.gov/Drugs/DrugSafety/DrugSafetyNewsletter/ucm115974.htm [December 31, 2017].
    1. Raisch DW, Rafi JA, Chen C, Bennett CL. Detection of cases of progressive multifocal leukoencephalopathy associated with new biologicals and targeted cancer therapies from the FDA's adverse event reporting system. Expert Opin Drug Saf. 2016;15(8):1003-1011.
    1. Zerbe CS, Marciano BE, Katial RK, et al. Progressive multifocal leukoencephalopathy in primary immune deficiencies: Stat1 gain of function and review of the literature. Clin Infect Dis. 2016;62(8):986-994.
    1. Gocmen R, Acar NP, Cagdas D, Kurne A. Progressive multifocal leukoencephalopathy in a patient with lymphoma and presumptive hyper IgE syndrome. J Neurovirol. 2017;23(4):632-636.

MeSH terms

Substances

LinkOut - more resources