Nivolumab for treatment of progressive multifocal leukoencephalopathy in Sézary syndrome

Graßl, Niklas; Bunse, Lukas; Beutel, Tatjana; Klockziem, Matti; Gass, Achim; Platten, Michael; Eisele, Philipp

doi:10.1111/ene.14433

Cited by 8 publications

(9 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In Patient 4 disease progression could not be stopped, demonstrated by rising copy numbers of JCV-DNA in CSF and increasing lesions on MRI. Similar catastrophic clinical courses have been published previously, including a young patient who was diagnosed early after mild symptoms developed and had low copy numbers of JCV-DNA in CSF at diagnosis [ 10 , 12 , 18 , 20 , 22 ]. This challenges the concept that the disease can be controlled if treatment was commenced early and raises the question, if the underlying immunodeficiency itself is a prognostic factor.…”

Section: Discussionsupporting

confidence: 73%

“…This is demonstrated by a median survival of 2 months in a case series of patients with in hematologic malignancies and stem-cell transplantation [27]. Checkpoint inhibition has been applied so far in 11 cases with nivolumab therapy and 20 cases with pembrolizumab therapy (including our previous report) with varying results [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Here were report on a series of 4 novel patients with PML in the context of PID or hematologic malignancy treated with pembrolizumab and follow-up data on one previously reported patient [21].…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, 31 published patients with PML have so far been treated with either pembrolizumab or nivolumab. Treatment outcomes range from moderate improvement of symptoms with stabilization to death from disease progression [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. To date, there are no clear prognostic factors to identify patients in whom checkpoint inhibition will be able to ameliorate PML [26].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pembrolizumab for treatment of progressive multifocal leukoencephalopathy in primary immunodeficiency and/or hematologic malignancy: a case series of five patients

et al. 2021

View full text Add to dashboard Cite

Progressive multifocal leukoencephalopathy is a rare opportunistic infection of the brain by John Cunningham polyomavirus in immune-compromised patients. In cases where no overt option for immune reconstitution is available [e.g., in patients with primary immunodeficiency (PID)], the disease is lethal in the majority of patients. Immune checkpoint inhibition has been applied in recent years with mixed outcomes. We present four novel patients and the follow-up of a previously published patient suffering from progressive multifocal leukoencephalopathy (PML) due to PID and/or hematologic malignancy who were treated with the immune checkpoint inhibitor pembrolizumab. In two patients with PID, symptoms improved and stabilized. One patient died because of worsening PML another of intracranial hemorrhage which was unrelated to PML or its treatment with pembrolizumab. The fifth patient suffered from PID and died of a pre-existing immune dysregulation, possibly exacerbated by pembrolizumab. The long-term follow-up of the first patient provides support for therapeutic decisions during this therapy and is the longest published clinical course of a patient with checkpoint inhibition for PML. We conclude that pembrolizumab can control PML symptoms long term in a subgroup of patients with PID, in our cases for 21 and 36 months. However, therapy must be started early because symptoms are only partially reversible. In light of severe adverse events, application of pembrolizumab is only justified if the prognosis for the individual patient is very poor.

show abstract

Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pembrolizumab for treatment of progressive multifocal leukoencephalopathy in primary immunodeficiency and/or hematologic malignancy: a case series of five patients

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In addition to the eight cases mentioned above, additional 13 individual case reports and two smaller case series (totaling 22 additional patients) were published during the course of the study on the use of PD-1 inhibitors in PML [53][54][55][56][57][58][59][60][61][62][63][64]. Eight of the 13 individual case reports described the use of pembrolizumab, and the remaining five publications used nivolumab.…”

Section: Anti-pd-1-antibodiesmentioning

confidence: 99%

Innovative therapeutic concepts of progressive multifocal leukoencephalopathy

et al. 2022

View full text Add to dashboard Cite

Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral disease of the brain—caused by human polyomavirus 2. It affects patients whose immune system is compromised by a corresponding underlying disease or by drugs. Patients with an underlying lymphoproliferative disease have the worst prognosis with a mortality rate of up to 90%. Several therapeutic strategies have been proposed but failed to show any benefit so far. Therefore, the primary therapeutic strategy aims to reconstitute the impaired immune system to generate an effective endogenous antiviral response. Recently, anti-PD-1 antibodies and application of allogeneic virus-specific T cells demonstrated promising effects on the outcome in individual PML patients. This article aims to provide a detailed overview of the literature with a focus on these two treatment approaches.

show abstract

“…The case report of Grassl et al [8]. in this issue raises other issues while maintaining the plausibility of checkpoint therapy for PML.…”

mentioning

confidence: 91%

Checkpoint therapy for progressive multifocal leukoencephalopathy: pointless?

Clifford

2020

Euro J of Neurology

View full text Add to dashboard Cite

Nivolumab for treatment of progressive multifocal leukoencephalopathy in Sézary syndrome

Cited by 8 publications

References 7 publications

Pembrolizumab for treatment of progressive multifocal leukoencephalopathy in primary immunodeficiency and/or hematologic malignancy: a case series of five patients

Pembrolizumab for treatment of progressive multifocal leukoencephalopathy in primary immunodeficiency and/or hematologic malignancy: a case series of five patients

Innovative therapeutic concepts of progressive multifocal leukoencephalopathy

Checkpoint therapy for progressive multifocal leukoencephalopathy: pointless?

Contact Info

Product

Resources

About