A current study examines the association between rituximab, a common lymphoma treatment and progressive multifocal leukoencephalitis (PML), a fast-moving and often fatal infection that attacks the white matter of the brain.
Hematologist and oncologist Charles Bennett, MD, of the Northwestern University Feinberg School of Medicine, is leading the project. In a recent issue of the journal Blood, he and his co-investigators reported on 57 cases, spanning from 1997 to 2008, in which patients with lymphoma, anemia, or rheumatoid arthritis developed PML after taking rituximab.
“People may think [PML is] early Alzheimer’s disease or depression,” Dr Bennett explained, noting that the infection often goes undiagnosed because the symptoms are so subtle at first. “Many of these patients have cancer and when they die, people assume it’s the cancer that killed them.”
Clinicians should look for forgetfulness, disorientation, mood changes, and any other strange neurological symptoms in individuals taking rituximab. In cases described by Dr Bennett, a brain biopsy and spinal tap confirmed the diagnosis of PML after a brain MRI and biopsy demonstrated a brain that appeared to have been eaten away. Rituximab has become the third monoclonal antibody to be associated with PML, according to a statement issued by Dr Bennett. The other 2 agents are Raptiva, which was taken off the market in April, and Tysabri, which was withdrawn from the market for 1.5 years because of similar concerns.
In lymphoma, rituximab binds to the CD20 protein, which is found on the outside of B-cell lymphomas. This action ultimately helps destroy the cancerous cell. “The drug has tremendous usefulness in lymphoma, but as its use expands to diseases that are not cancer, we might have to reconsider the risk benefit,” cautioned Dr Bennett.
“Some cancer patients take this drug chronically for nonfatal chronic leukemia, where the risk-benefit calculations differ from lymphoma.”
It’s not yet known how rituximab is connected to PML, or who may be at risk. Dr Bennett said the best available research exists in the area of lupus. In that patient population, an estimated 1 in 4000 develop PML.
Dr Bennett said the next step in the process is to determine the risk factors for PML in people who take rituximab. “We need to learn more about this. People have to think about the pros and cons in settings where it is being used for nonmalignant diseases,” he cautioned. People have been lulled into a false sense of security that this drug is harmless and that it only does good things. No drug is perfect.”
