Treatment of progressive multifocal Leukoencephalopathy associated with idiopathic lymphocytopenia with Nivolumab

Fischbach, Laura; Bauer, Tobias; Rüber, Theodor; Grobe‐Einsler, Marcus; Sitter, Aileen; Radbruch, Alexander; Kaut, Oliver

doi:10.1016/j.jns.2021.117503

Cited by 5 publications

(8 citation statements)

References 7 publications

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“…While PML without overt immunosuppression has been described in the literature, it is considered an exceedingly rare entity. [3–44] However, our single-center retrospective review suggests that PML without overt immunosuppression may make up a substantial proportion of PML cases (11.8%). Of note, prior population-based studies also reported no obvious immunocompromising disease or treatment in 6.3% [38] and 6.5% [45] of PML patients.…”

Section: Discussionmentioning

confidence: 99%

“…A comprehensive literature review of PML in the absence of overt immunosuppression (Table 1) [3–44,46] showed that previously described cases (median age 61 [range 21–81] years; 26% female) were usually found to have underlying comorbidities that may be associated with some degree of immunosuppression, including idiopathic CD4 lymphocytopenia (17/79; 21.5%), chronic renal failure (7/79; 8.9%) [5,22,26] and liver disease (15/70; 19%) most commonly due to hepatitis (6/79; 7.6%) [5,10] or alcoholism (6/79; 7.6%). [5,7,38,43] While case 2 had significant alcohol consumption in the year prior to diagnosis, both laboratory (liver function tests, coagulation studies) and radiographic (computed tomography abdomen) testing did not yield evidence for liver dysfunction.…”

Section: Discussionmentioning

confidence: 99%

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Progressive multifocal leukoencephalopathy without overt immunosuppression

Jain,

Branstetter,

Savaram

et al. 2023

Medicine

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Progressive multifocal leukoencephalopathy (PML) is a central nervous system disease caused by the human polyomavirus 2 that usually occurs in a setting of immunodeficiency. PML without overt immunosuppression is considered a rare occurrence but has been described in multiple previous case reports and series. Its prevalence, overall frequency, and prognosis are largely unknown. This is a single-center retrospective review of all University of Florida cases with the ICD10 PML diagnosis code (A81.2). PML without overt immunosuppression was defined as absence of human immunodeficiency virus (HIV) infection, hematological malignancy, immunomodulatory/-suppressive medications, autoimmune conditions with a propensity for PML (sarcoidosis, systemic lupus erythematosus). Cases that did not fulfill criteria for clinically or histologically definite PML were excluded. Of 52 patients with the ICD10 code A 81.2, 17 fulfilled definite diagnostic criteria for PML. Overt immunosuppression was identified in 15/17 (88.2%) cases (10/17 (58.8%): human immunodeficiency virus; 5/17 (29.4%): immunomodulatory/-suppressive medication). Two/seventeen (11.8%) cases were consistent with PML without overt immunosuppression. Possible contributing factors were a preceding dog bite and mild hypogammaglobulinemia M (39 mg/dL) in case 1 and significant alcohol use without evidence for liver disease in case 2. Both cases were fatal within 6 (case 1) and 2 (case 2) months. The results suggest that PML without overt immunosuppression may be more common than previously described. Therefore, PML should be considered even in the absence of overt immunosuppression if clinical and radiographic findings are suggestive of the diagnosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy without overt immunosuppression

Jain,

Branstetter,

Savaram

et al. 2023

Medicine

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“…Table 1 (detailed in Supplementary Table 1 ) summarizes published studies using the anti‐PD‐1 antibodies nivolumab and pembrolizumab in PML patients. 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 …”

Section: Restoration Of Immunity As a Treatment For Pmlmentioning

confidence: 99%

“…28,32 Table (detailed in Supplementary Table 1) summarizes published studies using the anti-PD-1 antibodies nivolumab and pembrolizumab in PML patients. [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] Anti-PD-1 therapies have shown promising results in some cases, with documented clinical and radiological benefit. In these patients, nivolumab or pembrolizumab seem to have triggered an effector response mediated by JCV-specific CD4 + and CD8 + T cells, 32,34 as well as immune reconstitution demonstrable on brain biopsy 36 and clearance of the virus in the CSF.…”

Section: Restoration Of Immunity As a Treatment For Pmlmentioning

confidence: 99%

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Advances in Treatment of Progressive Multifocal Leukoencephalopathy

Bernard‐Valnet

Koralnik

Pasquier

2021

Annals of Neurology

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Progressive multifocal encephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV), which occurs in immunocompromised individuals. Management of PML relies on restoration of immunity within the CNS. However, when this restoration cannot be readily achieved, PML has a grim prognosis. Innovative strategies have shown promise in promoting anti‐JCV immune responses, and include T‐cell adoptive transfer or immune checkpoint inhibitor therapies. Conversely, management of immune reconstitution inflammatory syndrome, particularly in iatrogenic PML, remains a major challenge. In this paper, we review recent development in the treatment of PML. ANN NEUROL 2021;90:865–873

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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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Treatment of progressive multifocal Leukoencephalopathy associated with idiopathic lymphocytopenia with Nivolumab

Cited by 5 publications

References 7 publications

Progressive multifocal leukoencephalopathy without overt immunosuppression

Progressive multifocal leukoencephalopathy without overt immunosuppression

Advances in Treatment of Progressive Multifocal Leukoencephalopathy

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

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