Pembrolizumab for the treatment of Progressive Multifocal Leukoencephalopathy (PML) in a patient with AIDS: A case report and literature review

Chatterjee, Tulika; Roy, Moni; Lin, Rone-Chun; Almoujahed, Mohammad O.; Ahmad, Sharjeel

doi:10.1016/j.idcr.2022.e01514

Cited by 5 publications

(3 citation statements)

References 18 publications

(36 reference statements)

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“… 39 Although there are no approved medications, experimental treatments involving ICIs and the application of virus specific allogenic T-cells have been utilized in treatment. 7 – 14 , 20 – 26 , 28 , 29 , 39 However, out of 91 PML patients treated with ICI, only 12 were related to AIDS. 20 Within this subgroup, 6 out of 12 patients died within a year, with causes including PML progression, PML-induced IRIS, and a combination of PML with other contributing diseases.…”

Section: Discussionmentioning

confidence: 99%

“… 4 Until recently, there were no effective treatment options for this often-fatal disease. Within the last years, the use of anti-PD-1 (programmed cell death protein 1) antibodies (immune checkpoint inhibitor, ICI), 5 – 20 and the application of allogeneic virus-specific T-cells 21 – 29 have shown encouraging treatment results for some PML patients. Notably, the absence of virus-specific T-lymphocytes in the blood has been identified as a negative prognostic factor in HIV-positive PML-patients.…”

Section: Introductionmentioning

confidence: 99%

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Combined treatment with allogeneic Epstein–Barr- and human polyomavirus 1 specific T-cells in progressive multifocal leukoencephalopathy and EBV infection: a case report

Nay,

Möhn,

Grote-Levi

et al. 2024

Ther Adv Neurol Disord

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Opportunistic viral infections in individuals with severe immunodeficiency can lead to fatal conditions such as progressive multifocal leukoencephalopathy (PML), for which treatment options are limited. These infections pose significant risks, especially when co-infections with other viruses occur. We describe a combined therapy approach using directly isolated allogeneic Human Polyomavirus 1 (also known as BKV) and Epstein–Barr virus (EBV) specific cytotoxic T-cells for the treatment of PML in conjunction with identified EBV in the cerebrospinal fluid (CSF) of a male patient infected with human immunodeficiency virus (HIV). A 53-year-old HIV-positive male, recently diagnosed with PML, presented with rapidly worsening symptoms, including ataxia, tetraparesis, dysarthria, and dysphagia, leading to respiratory failure. The patient developed PML even after commencing highly active antiretroviral therapy (HAART) 3 months prior. Brain magnetic resonance imaging (MRI) revealed multifocal demyelination lesions involving the posterior fossa and right thalamus suggestive of PML. In addition to the detection of human polyomavirus 2 (also known as JCV), analysis of CSF showed positive results for EBV deoxyribonucleic acid (DNA). His neurological condition markedly deteriorated over the following 2 months. Based on MRI, there was no evidence of Immune Reconstitution Inflammatory Syndrome contributing to this decline. The patient did not have endogenous virus-specific T-cells. We initiated an allogeneic, partially human leukocyte antigen-matched transfer of EBV and utilizing the cross-reactivity between BKV and JCV–BKV specific T-cells. This intervention led to notable neurological improvement and partial resolution of the MRI lesions within 6 weeks. Our case of a patient with acquired immune deficiency syndrome demonstrates that PML and concurrent EBV co-infection can still occur despite undergoing HAART treatment. This innovative experimental therapy, involving a combination of virus-specific T-cells, was demonstrated to be an effective treatment option in this patient.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combined treatment with allogeneic Epstein–Barr- and human polyomavirus 1 specific T-cells in progressive multifocal leukoencephalopathy and EBV infection: a case report

Nay,

Möhn,

Grote-Levi

et al. 2024

Ther Adv Neurol Disord

View full text Add to dashboard Cite

show abstract

“…In a small study of eight patients with PML treated with pembrolizumab, five had reduced JCV load, clinical and radiological improvement or stabilization and increased in vitro anti-JCV activity after treatment (71). Pembrolizumab, as a therapeutic strategy in PML, has also been described in many case reports, with encouraging results in some cases (72) and unfavorable in others (73). These controversial outcomes could be associated with several factors, such as time of diagnosis, underlying immunodeficiency, baseline JCV load, severity of neurological deficits before therapy, dose of pembrolizumab and time of treatment initiation.…”

Section: Latency Reversal and Augmentation Of Hiv-specific Cd8 + T-ce...mentioning

confidence: 99%

Immune Checkpoint Inhibitors and Infection: What Is the Interplay?

PAPADAKIS,

KARNIADAKIS,

MAZONAKIS

et al. 2023

In Vivo

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Progressive multifocal leukoencephalopathy in sarcoidosis successfully treated with pembrolizumab

Öztürk,

Tekeli,

Erdoğan

et al. 2024

J. Neurovirol.

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Pembrolizumab for the treatment of Progressive Multifocal Leukoencephalopathy (PML) in a patient with AIDS: A case report and literature review

Cited by 5 publications

References 18 publications

Combined treatment with allogeneic Epstein–Barr- and human polyomavirus 1 specific T-cells in progressive multifocal leukoencephalopathy and EBV infection: a case report

Combined treatment with allogeneic Epstein–Barr- and human polyomavirus 1 specific T-cells in progressive multifocal leukoencephalopathy and EBV infection: a case report

Immune Checkpoint Inhibitors and Infection: What Is the Interplay?

Progressive multifocal leukoencephalopathy in sarcoidosis successfully treated with pembrolizumab

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