Reports of Brain Virus from Common Cancer Drug
So far, 57 cases of an often fatal brain virus have been reported in association with administration of the cancer drug rituximab. The reports span 1997 to 2008, and include patients with anemia, rheumatoid arthritis and lymphoma, who developed the brain virus, progressive multifocal leukoencephalitis (PML).
Charles Bennett, M.D. and colleagues from the Northwestern University Feinberg School of Medicine are studying reports of PML in association with the cancer drug. Two such cases involving a New York lawyer and a Chicago woman are included in the study. Both developed the usually fatal brain virus while being treated for lymphoma and taking the most widely used drug to treat lymphoma, rituximab.
According to Dr. Bennett, "Rituximab is one of the most prominent drugs in a new class called monoclonal antibodies. It's now the third monoclonal antibody that is associated with PML.” The other cancer drug, Raptiva has been removed from the market because of the risk of the brain virus. Tysabri, also a cancer drug, was taken off the market for a year and a half because of suspicion that it might cause the deadly brain virus PML that eats away at the white matter of the brain rapidly.
Most frightening is that the brain virus may be overlooked. According to Dr. Bennett, "People may think it's early Alzheimer's disease or depression. Many of these patients have cancer and when they die, people assume it's the cancer that killed them”, suggesting that the incidence of deaths from the PML brain virus may be much higher than is reported.
In the case of the New York, lawyer and Chicago woman, MRI and brain biopsy were performed when they suddenly experienced cognitive decline. The tests revealed their brains appeared to be eaten away. Spinal tap revealed the diagnosis of the brain virus PML.
Dr. Bennett says no one knows the real connection between the PML brain virus and rituximab. The cancer drug is also used off-label to treat multiple sclerosis, lupus, and anemia from autoimmune disease. Rituximab is also approved by the FDA for the treatment of rheumatoid arthritis.
Dr. Bennett is head of the RADAR project (Research on Adverse Drug Events and Reports), an international effort to identify dangerous reactions to medications and devices. To uncover the previously unknown cases of the PML brain virus, Dr. Bennett solicited information from physicians at 12 major cancer centers around the country. He offered to write the reports about the information he obtained from the cancer centers, related to rituximab and the brain virus. He found 22 new cases.
Dr. Bennett says, “It’s a lot of work to produce these reports”, explaining the reason why he had not seen documentation of the brain virus associated with the cancer drug rituximab until now.
Patients taking rituximab who develop symptoms of forgetfulness, confusion, or mood changes should report to their doctor. Physicians are urged to be aware of the possibility of the brain virus, and report neurologic changes that occur in patients being treated with the drug. No one knows who is at risk, or how the cancer drug rituximab and the brain virus are connected.
Blood, 14 May 2009, Vol. 113, No. 20, pp. 4834-4840.