Nicolas Lambert1,2, Majdouline El Moussaoui3, Pierre Maquet1,4. 1. Department of Neurology, Liège University Hospital, Liège, Belgium. 2. GIGA-Stem Cells, Molecular regulation of neurogenesis, University of Liège, Liège, Belgium. 3. Department of General Internal Medicine and Infectious Diseases, Liège University Hospital, Liège, Belgium. 4. GIGA-CRC in vivo imaging, University of Liège, Liège, Belgium.
Abstract
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: 35 patients were included in the present study. 21 of them reportedly benefited from the treatment. Age, blood CD4+ cells count, pre-treatment 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 the CSF and reduction of the lesion load on magnetic resonance imaging after ICI administration were 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 raise the issue of the optimal management of irAEs during ICI treatment in this setting. This article is protected by copyright. All rights reserved.
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: 35 patients were included in the present study. 21 of them reportedly benefited from the treatment. Age, blood CD4+ cells count, pre-treatment 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 the CSF and reduction of the lesion load on magnetic resonance imaging after ICI administration were 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 raise the issue of the optimal management of irAEs during ICI treatment in this setting. This article is protected by copyright. All rights reserved.
Authors: Nicolas Lambert; Majdouline El Moussaoui; Caroline Ritacco; Martin Moïse; Astrid Paulus; Philippe Delvenne; Frédéric Baron; Bernard Sadzot; Pierre Maquet Journal: Front Immunol Date: 2022-05-03 Impact factor: 8.786