Saudi Journal of Kidney Diseases and Transplantation

: 2019  |  Volume : 30  |  Issue : 4  |  Page : 998--999

Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy

Ajit Venniyoor 
 National Oncology Center, The Royal Hospital, Post Box 1331, Seeb, Postal Code 111, Muscat, Sultanate of Oman

Correspondence Address:
Ajit Venniyoor
National Oncology Center, The Royal Hospital, Post Box 1331, Seeb, Postal Code 111, Muscat
Sultanate of Oman

How to cite this article:
Venniyoor A. Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy.Saudi J Kidney Dis Transpl 2019;30:998-999

How to cite this URL:
Venniyoor A. Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2020 Sep 22 ];30:998-999
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Full Text

To the Editor,

The Guru et al[1] study (Saudi J Kidney Dis Transpl 2019;30(2):526-30) describes a case of progressive multifocal leukoencephalopathy (PML) occurring in a renal transplant patient who subsequently expired. They have listed the limited options available for treatment but note a uniformly fatal outcome with a median survival of 6.4 months. Cortese et al[2] article published in the New England Journal of Medicine reported a significant advance in treatment of this disease, with the use of immune checkpoint inhibitors (CPi) – pembro-lizumab and nivolumab. These drugs are Food and Drug Administration approved for immuno-therapy of multiple cancers. The interaction between Programmed cell death protein 1 (PD-1) (on the cytotoxic T-cells) and programmed death ligand 1 (PD-L1) (on the tumor cells) induce immune tolerance for the cancer cells; CPi block this interaction and invigorate the antitumor activity of T-cells. Three groups[2],[3],[4] reported the use of these drugs in treatment of PML arising in 10 patients of hematological disorders or HIV infection. Seven of them improved to varying degrees, and as the editorial notes,[5] the presence of JC virus-specific T-cells in the blood appears to be a prerequisite for their use, something not reported in this case. Other success stories have appeared in recent literature.[6] These series however did not include any organ transplant patients, and it would be interesting to see whether CPi work in this group without significant adverse events. CPi are relatively contraindicated in patients on steroids [such as those with autoimmune disorders and organ transplant, as steroids may (theoretically) prevent the immune stimulation] but have been used in transplant patients for treatment of malignancies, with both tumor regression and graft rejection[7]. Hence, the risk to benefit ratio must be carefully considered before using CPi for PML in transplant patients. Interestingly, CPi themselves are associated with PML.[8]

Conflict of interest: None declared.


1Guru PK, Vissing MB, Agarwal A, Krishna M. Biopsy-proven progressive multifocal leukoencephalopathy in a renal transplant patient. Saudi J Kidney Dis Transpl 2019;30: 526-30.
2Cortese I, Muranski P, Enose-Akahata Y, et al. Pembrolizumab treatment for progressive multifocal leukoencephalopathy. N Engl J Med 2019;380:1597-605.
3Walter O, Treiner E, Bonneville F, et al. Treatment of progressive multifocal leuko- encephalopathy with nivolumab. N Engl J Med 2019;380:1674-6.
4Rauer S, Marks R, Urbach H, et al. Treatment of progressive multifocal leukoencephalopathy with pembrolizumab. N Engl J Med 2019;380: 1676-7.
5Koralnik IJ. Can immune checkpoint inhibitors keep JC virus in check? N Engl J Med 2019; 380:1667-8.
6Hoang E, Bartlett NL, Goyal MS, Schmidt RE, Clifford DB. Progressive multifocal leuko-encephalopathy treated with nivolumab. J Neurovirol 2019;25:284-7.
7De Bruyn P, Van Gestel D, Ost P, et al. Immune checkpoint blockade for organ transplant patients with advanced cancer: How far can we go? Curr Opin Oncol 2019;31:54-64.
8Martinot M, Ahle G, Petrosyan I, et al. Progressive multifocal leukoencephalopathy after treatment with nivolumab. Emerg Infect Dis 2018;24:1594-6.