Progressive multifocal leukoencephalopathy associated with a lymphoproliferative disorder treated with pembrolizumab

Holmes, Alex; Wellings, Tom; Walsh, Oliver; Rowlings, Philip

doi:10.1007/s13365-020-00899-0

Cited by 14 publications

(17 citation statements)

References 8 publications

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“…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%

“…Nevertheless, autoimmune phenomena (e.g., diarrhea, pneumonitis) as a result of checkpoint inhibition is frequently being observed in cancer patients. Autoimmune adverse reactions, such as myositis, rashes and worsening of a pre-existing digestive tract granulomatosis, have been reported in PML patients [ 14 , 23 , 25 ]. None of the previously published PML patients experienced autoimmune cytopenia after treatment with pembrolizumab or nivolumab, despite one of the patients suffered from autoimmune thrombocytopenia before development of PML [ 10 , 16 , 20 , 24 ].…”

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%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…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

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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.

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“…We found 20 articles (14 case reports and six case series) reporting a total of 37 patients who received an ICI in order to treat PML [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. One patient was excluded from the present report because PML had already stabilized before ICI administration [3] and another patient because reported data were insufficient to determine the eventual clinical course [13].…”

Section: Re Sultsmentioning

confidence: 99%

Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy: Identifying relevant outcome factors

Lambert

Moussaoui²,

Maquet

2021

Euro J of Neurology

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Introduction Progressive multifocal leukoencephalopathy (PML) is an infectious brain disease caused by JC virus in immunocompromised individuals. Immune checkpoint inhibitors (ICIs) recently emerged as a therapeutic hope for these patients but identification of those likely to respond to the treatment is still an unmet need. Method We performed a systematic PubMed search for reports of patients treated for PML using an ICI. Clinical, biological and radiological characteristics were contrasted between patients who responded to the treatment (RP) and those who did not (NRP). Results Thirty‐five patients were included in the present study. Twenty‐one of them reportedly benefited from the treatment. Age, blood CD4+ cells count, pretreatment viral load in the cerebrospinal fluid (CSF), PML lesions localization, treatment delay since first PML symptoms, type of ICI used and immune‐related adverse events (irAEs) occurrence did not significantly differ between RP and NRP. By contrast, a history of therapeutic immune suppression and the use of an immunosuppressive therapy at treatment initiation were significantly associated with a poor response. Besides, reaching an undetectable viral load in the CSF and reduction of the lesion load on magnetic resonance imaging after ICI administration was associated with a good clinical response. Conclusion Current data suggest that patients with PML under immunosuppressive therapy are less likely to respond to ICIs and raises the issue of the optimal management of irAEs during ICI treatment in this setting.

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Progressive multifocal leukoencephalopathy associated with a lymphoproliferative disorder treated with pembrolizumab

Cited by 14 publications

References 8 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

Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy: Identifying relevant outcome factors

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