Atezolizumab Treatment for Progressive Multifocal Leukoencephalopathy

Lambert, Nicolas; Dauby, Solène; Dive, Dominique; Sadzot, Bernard; Maquet, Pierre

doi:10.3201/eid2801.204809

Cited by 7 publications

(3 citation statements)

References 10 publications

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“…A close clinical follow-up is therefore essential when a patient is started on this therapeutic class to detect adverse events promptly. Since treatment of these usually relies on corticosteroids, which impairs anti-JCV immunity, benefits expected from treating IRIS and irAEs must be balanced with the risk of favoring PML progression ( 3 ). To date, the optimal management for these complex clinical situations is still unknown and should be further investigated.…”

Section: Discussionmentioning

confidence: 99%

“…These innovative therapies enable durable clinical response for a subset of patients with unresectable malignancies, including advanced non-small cell lung cancer (NSCLC), which is the largest single contributor of cancer deaths in the United States ( 1 ). More recently, ICIs targeting programmed cell death 1 (PD1) or its ligand (PD-L1) were proposed for the treatment of progressive multifocal leukoencephalopathy (PML) ( 2 , 3 ). The latter is a devastating brain infectious disease caused by JC virus (JCV) in the course of cellular immune deficiency.…”

Section: Introductionmentioning

confidence: 99%

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Killing Two Birds With One Stone: Effective Control of Both Non-Small Cell Lung Cancer and Progressive Multifocal Leukoencephalopathy With Atezolizumab, A Case Report

et al. 2022

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Treating patients with cancer complicated by severe opportunistic infections is particularly challenging since classical cancer treatments, such as chemotherapy, often induce profound immune suppression and, as a result, may favor infection progression. Little is known about the potential place of immune checkpoint inhibitors in these complex situations. Here, we report a 66-year-old man who was concomitantly diagnosed with non-small cell lung cancer and progressive multifocal leukoencephalopathy. The patient was treated with anti-PD-L1 antibody atezolizumab, which allowed effective control of both lung cancer and progressive multifocal leukoencephalopathy, as demonstrated by the patient’s remarkable neurologic clinical improvement, JC viral load reduction in his cerebrospinal fluid, regression of the brain lesions visualized through MRI, and the strict radiological stability of his cancer. In parallel, treatment with atezolizumab was associated with biological evidence of T-cell reinvigoration. Hence, our data suggest that immune checkpoint inhibitors may constitute a treatment option for patients with cancer complicated by severe opportunistic infections.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Killing Two Birds With One Stone: Effective Control of Both Non-Small Cell Lung Cancer and Progressive Multifocal Leukoencephalopathy With Atezolizumab, A Case Report

et al. 2022

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“…As there is no antiviral treatment proven effective for PML, the prognosis mainly relies on the ability to achieve timely immune reconstitution. In this line, several strategies aimed at reinvigorating anti-HPyV2 immune activity have recently emerged, including the use of immune checkpoint inhibitors, human recombinant interleukin 7, and polyomavirus-specific T-cell transfer [ 28 , 29 , 30 , 31 , 32 , 33 ].…”

Section: Clinical Experience In Cns Infectionsmentioning

confidence: 99%

Virus-Specific T-Cell Therapy for Viral Infections of the Central Nervous System: A Review

Lambert

Moussaoui

Baron

et al. 2023

Viruses

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Opportunistic viral infections of the central nervous system represent a significant cause of morbidity and mortality among an increasing number of immunocompromised patients. Since antiviral treatments are usually poorly effective, the prognosis generally relies on the ability to achieve timely immune reconstitution. Hence, strategies aimed at reinvigorating antiviral immune activity have recently emerged. Among these, virus-specific T-cells are increasingly perceived as a principled and valuable tool to treat opportunistic viral infections. Here we briefly discuss how to develop and select virus-specific T-cells, then review their main indications in central nervous system infections, including progressive multifocal leukoencephalopathy, CMV infection, and adenovirus infection. We also discuss their potential interest in the treatment of progressive multiple sclerosis, or EBV-associated central nervous system inflammatory disease. We finish with the key future milestones of this promising treatment strategy.

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Promise and Challenges of Checkpoint Inhibitor Therapy for Progressive Multifocal Leukoencephalopathy in HIV

2022

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Purpose of Review Progressive multifocal leukoencephalopathy (PML) is a severe opportunistic infection that remains an important cause of morbidity and mortality in people living with HIV (PLWH). Immune checkpoint molecules are negative regulators of the immune response that have been targeted as a strategy to bolster anti-viral immunity in PML, with varied outcomes reported. While initiation and optimization of antiretroviral therapy remains the standard of care in HIV-related PML, the specific opportunities and risks for checkpoint blockade in these cases should be explored. Recent Findings As of April 15, 2022, only 5 of the 53 total published cases of PML treated with checkpoint blockade had underlying HIV infection; four of these had a favorable outcome. The risk of promoting immune reconstitution inflammatory syndrome is a major concern and underscores the importance of patient selection and monitoring. Summary Checkpoint blockade warrants further exploration as a potentially promising option for treatment escalation in HIV-related PML.

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Atezolizumab Treatment for Progressive Multifocal Leukoencephalopathy

Cited by 7 publications

References 10 publications

Killing Two Birds With One Stone: Effective Control of Both Non-Small Cell Lung Cancer and Progressive Multifocal Leukoencephalopathy With Atezolizumab, A Case Report

Killing Two Birds With One Stone: Effective Control of Both Non-Small Cell Lung Cancer and Progressive Multifocal Leukoencephalopathy With Atezolizumab, A Case Report

Virus-Specific T-Cell Therapy for Viral Infections of the Central Nervous System: A Review

Promise and Challenges of Checkpoint Inhibitor Therapy for Progressive Multifocal Leukoencephalopathy in HIV

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