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Pembrolizumab Holds Promise for Patients With Rare, Fatal Brain Infection

Drug Improved or Stabilized Symptoms, Shrank Brain Lesions

Anti-cancer drug pembrolizumab could delay the progression of progressive multifocal leukoencephalopathy (PML), a brain infection caused by the JC virus (JCV) that usually proves fatal. The study by scientists at the National Institute of Neurological Disorders and Stroke was recently published in the New England Journal of Medicine.

Pembrolizumab blocks the interaction between the PD-1 and PD-L1 proteins, which typically prevent the immune system from causing excessive inflammation. But some tumors that have PD-L1 on their surface can exploit this "off switch," reducing the immune system’s ability to attack the cancer. Recent studies of patients with PML indicate that the process may also occur in JCV brain infections.

Eight patients with worsening PML were treated with pembrolizumab. Their infection status was monitored by MRI brain scans and by checking JCV levels in their cerebral spinal fluid. In five patients, pembrolizumab reduced the amount of circulating virus. Moreover, their symptoms improved or stabilized, and MRIs showed that their infection-related brain lesions were shrinking.

JCV, a common and usually harmless virus, is typically found in the kidneys of up to two-thirds of the population. On rare occasion, in patients with suppressed immune systems, the virus can modify and cause infection in brain cells. These infections cause PML, which can lead to clumsiness, progressive weakness, and changes in vision, speech, and personality.

Researchers are working on discovering markers for individuals at high risk for PML and for earlier detection of infection.

Source: National Institutes of Health, April 11, 2019

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