The use of checkpoint inhibitors for therapy of progressive multifocal leucoencephalopathy is amazing, or frightening, to say the least. This is a deadly brain infection which is very rare. It became somewhat more common when the therapy of HIV infection was in its early days. Many AIDS patients perished of this viral infection caused by the polyoma vírus. Then it disappeared again. It came up in neurology again because it is a relatively common complication of therapy with monoclonal antibodies, especially, but not only natalizumab. Hundreds of patients developed PML, as it is known within circles of specialists, patients and families.
One of the principles of medical therapy is that you should try to avoid having to use a medication to treat a side-effect of another medication. It is somewhat like people who are blind drunk and snort cocaine to become sexually able, or to drive. Or people who have to take steroids because of allergies to drugs used in chronic diseases, like lamotrigine for epilepsy or bipolar disease.
The rule that all physicians follow is to stop the drug that caused the problem. In the case of PML this is a recourse that does not help patients much, because when it is discovered, the cerebral damage is extensive and irreversible. Now the pharmaceutic industry has come up with the possibility that pembrolizumab, one of the new class of checkpoint inhibitors with the comercial name Keytruda, has helped cerebral lesions of PML in 2 cases of 5 who showed some response, of 8 who were treated for PML.
Kurt Samson. Neurology Today May 23, 2019, issue 10.
Cortese et al. N Engl J Med. Published online April 10, 2019. doi: 10.1056/NEJMoa1815039.
This is a horrible scenario. The young woman has a neurological deficit because of multiple sclerosis, a disease that does not threaten life. In protocols made up by many national authorities, she is given interferons and does not respond. The déficits usually evolve over many months or a few years. She is offered natalizumab, improves a little, until PML comes. She becomes bed-ridden, unconscious or demented, incontinent, frequently in intensive care units. The care of PML costs many thousands of dollars. The fact that this dark scenario may be made worse by the cost of another monoclonal antibody, of a new class called checkpoint inhibitors, is the script of a horror movie.
But it is precisely what is being offered.
Dr Paulo Bittencourt
