000 02475nab a2200241 4500
999 _c13036
_d13036
003 CO-MdCUR
005 20190605140613.0
008 170814s xxu||||| |||| 00| 0 eng d
040 _cRemington
_aCO-MdCUR
_erda
082 _221
773 0 _011137
_923640
_aMassachusetts Medical Society
_dBoston, Massachusetts Medical Society.
_o20312
_tThe New England journal of medicine.
_w11137412
_x0028-4793
100 1 _939635
_aCortese, Irene
245 _aPembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy
264 _aBoston:
_bMassachusetts Medical Society,
_c2019.
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
700 1 _939637
_aEnose-Akahata, Yoshimi
942 _2ddc
_cBK