000 | 02475nab a2200241 4500 | ||
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_c13036 _d13036 |
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003 | CO-MdCUR | ||
005 | 20190605140613.0 | ||
008 | 170814s xxu||||| |||| 00| 0 eng d | ||
040 |
_cRemington _aCO-MdCUR _erda |
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082 | _221 | ||
773 | 0 |
_011137 _923640 _aMassachusetts Medical Society _dBoston, Massachusetts Medical Society. _o20312 _tThe New England journal of medicine. _w11137412 _x0028-4793 |
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100 | 1 |
_939635 _aCortese, Irene |
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245 | _aPembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy | ||
264 |
_aBoston: _bMassachusetts Medical Society, _c2019. |
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300 | _a1597 - 1606 | ||
520 | 3 | _aBACKGROUND Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain infection that is caused by the JC virus and is typically fatal unless immune function can be restored. Programmed cell death protein 1 (PD-1) is a negative regulator of the immune response that may contribute to impaired viral clearance. Whether PD-1 blockade with pembrolizumab could reinvigorate anti–JC virus immune activity in patients with PML was unknown. METHODS We administered pembrolizumab at a dose of 2 mg per kilogram of body weight every 4 to 6 weeks to eight adults with PML, each with a different underlying predisposing condition. Each patient received at least one dose but no more than three doses. RESULTS Pembrolizumab induced down-regulation of PD-1 expression on lymphocytes in peripheral blood and in cerebrospinal fluid (CSF) in all eight patients. Five patients had clinical improvement or stabilization of PML accompanied by a reduction in the JC viral load in the CSF and an increase in in vitro CD4+ and CD8+ anti–JC virus activity. In the other three patients, no meaningful change was observed in the viral load or in the magnitude of antiviral cellular immune response, and there was no clinical improvement. CONCLUSIONS Our findings are consistent with the hypothesis that in some patients with PML, pembrolizumab reduces JC viral load and increases CD4+ and CD8+ activity against the JC virus; clinical improvement or stabilization occurred in five of the eight patients who received pembrolizumab. Further study of immune checkpoint inhibitors in the treatment of PML is warranted. (Funded by the National Institutes of Health.) | |
700 | 1 |
_939636 _aMuranski, Pawel |
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700 | 1 |
_939637 _aEnose-Akahata, Yoshimi |
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942 |
_2ddc _cBK |