Philadelphia – Adoptive transfer of donor-derived T cells represents a potentially life-saving treatment of severely immunocompromised patients with progressive multifocal leukoencephalopathy (PML).
Courtesy NIH/NINDS
Dr. Erin Beck
“We think this strategy has real potential to be one of the first effective treatments for PML,” Erin Beck, MD, PhD, said during a press conference at the annual meeting of the American Academy of Neurology.
In a pilot study including 12 patients with PML, the 7 who survived had substantial neurological improvement after treatment with this immunotherapeutic approach, said Dr. Beck of the National Institute of Neurological Disorders and Stroke.
“This was very encouraging to us because these patients were worsening at the time of their treatment and we did not expect them to do well,” she said.
There were no serious adverse events related to treatment, which suggests the approach is safe for patients with PML, according to Dr. Beck.
“This is a phenomenal breakthrough,” Natalia S. Rost, MD, MPH, chair of the meeting’s science committee, said at the press conference. “Giving a diagnosis of PML to a patient is basically giving them a death sentence, and it’s one of the most dreaded scenarios in our clinical practice.”
PML, an opportunistic infection of the central nervous system caused by JC polyomavirus, is usually fatal unless adaptive immunity to JC polyomavirus can be restored, Dr. Beck said.
Cases of PML surged in the 1980s and 1990s as a result of the HIV/AIDS epidemic, she said, and an increase in cases has been observed more recently related to new immunosuppressive treatments for cancer and autoimmune diseases.
The pilot study described by Dr. Beck included 12 patients with refractory PML who underwent adoptive transfer of polyomavirus-specific T cells (PyVSTs) that were generated from partially matched first-degree relatives of the patients. Up to three infusions were given at least 28 days apart.
Although five patients died of PML, the remaining seven patients stabilized and in some cases experienced significant neurological improvement, according to the investigators. Two of the seven died of PML a year after their final infusion.
No overt immune reconstitution inflammatory syndrome (IRIS) was observed in treated patients.
It’s not clear to date which PML patients may be most likely to benefit from this treatment approach because there were no differences in age, sex, baseline leukocyte count numbers, or time since their initial diagnosis between responders and nonresponders, Dr. Beck said.
However, patients who died tended to have much higher JC virus copy numbers in their spinal fluid, as did some patients who were enrolled but died before they could receive any treatment, she added.
“That high range, I think, is a very bad prognostic sign,” Dr. Beck said. “A number in the lower range doesn’t mean a good prognosis, but it means potentially that you could respond to a treatment such as this one.”
The study was funded by National Institute of Neurological Disorders and Stroke. The investigators disclosed no conflicts related to the study.
SOURCE: Cortese I et al. AAN 2019, Abstract Plen01.002.