Rare Disease Report

Treating PML with Adoptive T-cell Therapy

NOVEMBER 14, 2018
Rachel Lutz
Adoptive T-cell therapy can treat a rare and fatal brain infection called progressive multifocal leukoencephalopathy (PML), according to a recent study. The infection often occurs in patients with cancer and other patients with compromised immune systems. PML attacks the brain’s white matter and is linked with altered mental status, motor deficits, ataxia, and visual symptoms. Although there are a few treatments, they produce poor results.

Investigators from the University of Texas MD Anderson Cancer Center wrote a case report of 3 separate patients in order to report the success of their adoptive T-cell treatment approach.

“There is no effective therapy for PML, and patients with PML have a dismal outcome (worse than many types of cancer),” study author Katy Rezvani, MD, PhD, told Rare Disease Report®. “Our study was the first example of patients receiving third-party viral specific T-cells for the treatment of PML.”

The JC virus, implicated in causing PML, and the BK both belong to the Polyomaviridae family. Because other research groups have treated BK virus infections with adoptive T-cell treatment, the MD Anderson investigators believed the viruses were genetically similar enough that the treatment would work well with JC virus as well.

Patient 1 included in the case study was a 32-year-old woman with acute myeloid leukemia (AML) who had previously received a cord blood transfusion. Patient 2 was a 73-year-old female with a blood disorder causing over-production of red cells. She was treated with ruxolitinib. Patient 3 was a 35-year-old man with AIDS who had discontinued his aggressive HAART therapy due to side effects; he was unable to walk.

Each of the patients underwent an initial BK virus-specific T cell infusion. After that, the investigators observed a reduction in JC viral load in their cerebrospinal fluid. Patient 1 dropped from 700 to 78 copies/mL; Patient 2 reduced from 230,000 to 5,200 c/mL; and Patient 3 dropped from 4,300 to 1,300 c/mL.

Patients 1 and 3 showed clinical improvement in their JC virus and their responses, despite immunodeficiency, according to the investigators. There were no infusion-related reactions.

“This approach can target JCV and PML irrespective of the underlying disease, as demonstrated by the differences in the underlying conditions of the three patients treated in this study,” Dr. Rezvani said. “All 3 patients had a significant reduction on the JCV load in their CNS and in patients 1 and 2, we observed significant clinical benefit.”

All 3 patients underwent additional treatment. Patient 1 had 2 more infusions which cleared the virus in the CSF and the patient had no evidence of PML at 27 months from the first infusion. Patient 2 received a second infusion, but there was no further improvement noted, the investigators said. She died at 8 months from the first infusion. Patient 3, received more infusions which cleared the JC virus, and he regained mobility; 9 months from the first infusion he was able to walk with a cane.

“If our results are confirmed in a larger group of patients, we hope to obtain US Food and Drug Administration approval for the BKV product so that we can make it available to all patients with PML. Our approach of cellular immunotherapy for the treatment of patients highlights the power of immunotherapy to treat this disease,” Dr. Rezvani concluded.

The study, “Allogeneic BK Virus–Specific T Cells for Progressive Multifocal Leukoencephalopathy,” was published in The New England Journal of Medicine.

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