Literature Review

Virus-Specific T-Cell Infusions May Resolve Progressive Multifocal Leukoencephalopathy

Two of three patients cleared JC virus from CSF after infusion.


 

Infusion of allogeneic BK virus-specific T cells may be an effective treatment for patients with progressive multifocal leukoencephalopathy (PML), according to a report in the October 11 New England Journal of Medicine. The infusion cleared JC virus from the CSF of two patients and reduced viral load in the third, reported lead author Muharrem Muftuoglu, MD, of the Department of Stem Cell Transplantation and Cellular Therapy at the University of Texas MD Anderson Cancer Center in Houston, and colleagues. One of the patients completely recovered and returned to work; this outcome was unprecedented in PML therapy.

“Several approaches for the treatment of PML, including the use of antiviral medications and mirtazapine, have been tested, with poor results,” the investigators said. Although virus-specific T-cell infusion is a novel approach to treating PML, this method has been used for other conditions. “Several groups, including ours, have successfully used viral-specific T cells to treat BK virus infection after stem-cell transplantation,” the investigators said. “Because BK virus and JC virus are genetically similar to one another and share a number of immunogenic proteins with a substantial degree of sequence homology ... we hypothesized that T cells developed against BK virus may also be effective against JC virus infection.”

This hypothesis proved correct. The investigators infused three patients with PML with “cryopreserved, third-party–produced, viral-specific T cells that had been designed for the treatment of patients with BK virus infection after stem-cell transplantation.” Each patient presented with a different condition and PML-precipitating therapy. The first patient was a 32-year-old woman with high-risk acute myeloid leukemia who had received a cord-blood transplantation, the second a 73-year-old woman with JAK2-positive myeloproliferative neoplasia on ruxolitinib therapy, and the third a 35-year-old man with HIV who had received highly active antiretroviral therapy.

T-cell infusions cleared JC virus from the CSF of the woman with leukemia (three infusions) and the man with HIV (four infusions). These patients recovered to different degrees.The woman had full resolution of symptoms, while the man had slurred speech and walked with a cane. Treatment reduced JC viral load in the elderly woman with myeloproliferative neoplasia (two infusions), but she did not clear the virus and died about eight months later.

No adverse events occurred, but two patients developed immune reconstitution inflammatory syndrome. This outcome was likely caused by the T-cell infusion, since absolute T-cell counts remained steady and white matter enhancement was detected on MRI within four weeks of treatment. Still, the investigators were optimistic about future potential.

“Third-party–produced, ‘off-the-shelf,’ partially HLA-matched, BK virus–specific T cells may serve as therapy for PML,” the investigators concluded. “Further study in a larger group of patients is required to determine the success rate, durability, and longer-term adverse events associated with this treatment.”

The study was funded by the MD Anderson Cancer Center Moon Shots Program and the National Institutes of Health.

—Will Pass

Suggested Reading

Muftuoglu M, Olson A, Marin D, et al. Allogeneic BK specific T cells for progressive multifocal leukoencephalopathy. N Engl J Med. 2018;379(15):1443-1451.

Next Article: