Effectiveness of Immune Checkpoint Inhibitors in Transplant Recipients with Progressive Multifocal Leukoencephalopathy

Medrano, Chloé; Vergez, François; Mengelle, Catherine; Faguer, Stanislas; Kamar, Nassim; Bello, Arnaud Del

doi:10.3201/eid2511.190705

Cited by 24 publications

(29 citation statements)

References 5 publications

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“…Contrasting results were observed in another study, three kidney transplant recipients suffering from PML were treated with nivolumab and all three patients died within 8 weeks with evidence of disease progression. 49 As an explanation for this adverse outcome, 48 the authors speculate that immunosuppressive therapy (ie, calcineurin inhibitors) might have led to persistent T cell dysfunction and lymphopenia. The authors further point out that patients with severe lymphopenia also did not respond favorably to ICI treatment.…”

Section: Progressive Multifocal Leukoencephalopathymentioning

confidence: 99%

On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19

Gambichler

Reuther

Scheel

et al. 2020

J Immunother Cancer

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The present review summarizes up-to-date evidence addressing the frequently discussed clinical controversies regarding the use of immune checkpoint inhibitors (ICIs) in cancer patients with viral infections, including AIDS, hepatitis B and C, progressive multifocal leukoencephalopathy, influenza, and COVID-19. In detail, we provide available information on (1) safety regarding the risk of new infections, (2) effects on the outcome of pre-existing infections, (3) whether immunosuppressive drugs used to treat ICI-related adverse events affect the risk of infection or virulence of pre-existing infections, (4) whether the use of vaccines in ICI-treated patients is considered safe, and (5) whether there are beneficial effects of ICIs that even qualify them as a therapeutic approach for these viral infections.

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Section: Progressive Multifocal Leukoencephalopathymentioning

confidence: 99%

On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19

Gambichler

Reuther

Scheel

et al. 2020

J Immunother Cancer

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“…Perhaps unsurprisingly, patients treated early seemed to do better than those treated with late-stage disease. A case series of nivolumab usage in three patients with kidney transplants and PML showed poor outcomes, with all three dying shortly after diagnosis (Medrano et al, 2019). Interestingly, these three patients and the three patients with no clinical improvement described by Cortese et al (2019) all had significant lymphopenia, suggesting the use of immune checkpoint blocking antibodies may be limited in this subset of patients.…”

Section: Immune Checkpoint Blocking Antibodies: Nivolumab and Pembrolmentioning

confidence: 99%

Novel treatments for progressive multifocal leukoencephalopathy

Bennett

Fernandes

2020

Br J Hosp Med

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Progressive multifocal leukoencephalopathy is a rare demyelinating disorder of the CNS, caused by John Cunningham virus, that occurs in those with impaired immune systems. Existing treatment options are ineffective or unproven. This article reviews research into novel therapies: immune checkpoint-blocking antibodies (nivolumab and pembrolizumab), allogenic BK virus-specific T cell treatment and filgrastim. Results for these therapies in small clinical trials are promising, but further research is required to assess efficacy fully.

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“…Six months after transplantation, the infection risk starts to decrease and the most frequently encountered pathogens are EBV, Cryptococcus neoformans and JC virus, that can lead to PML, which is a fatal neurological condition characterized by subcortical white matter lesions with different neurological manifestations and without any effective treatment [57]. Nivolumab, a monoclonal antibody against PD-1 (programmed death-1), failed to obtain any improvement in transplant recipients [58], although stopping or reducing immunosuppressive drugs was successful in some cases [59]. Notably, infusion of allogeneic BK virus-specific T cells achieved alleviation of clinical signs and clearance/ reduced load of JC virus in the cerebrospinal fluid (CSF) in two immunosuppressed patients [60].…”

Section: Infectionsmentioning

confidence: 99%

Immunosuppression-related neurological disorders in kidney transplantation

et al. 2021

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A large number of neurological disorders can affect renal transplant recipients, potentially leading to disabling or life-threatening complications. Prevention, early diagnosis and appropriate management of these conditions are critical to avoid irreversible lesions. A pivotal role in the pathogenesis of common post-transplant neurological disorders is played by immunosuppressive therapy. The most frequently administered regimen consists of triple immunosuppression, which comprises a calcineurin inhibitor (CNI), a purine synthesis inhibitor and glucocorticoids. Some of these immunosuppressive drugs may lead to neurological signs and symptoms through direct neurotoxic effects, and all of them may be responsible for the development of tumors or opportunistic infections. In this review, after a brief summary of neurotoxic pathogenetic mechanisms encompassing recent advances in the field, we focus on the clinical presentation of more common and severe immunosuppression-related neurological complications, classifying them by characteristics of urgency and anatomic site. Our goal is to provide a general framework that addresses such clinical issues with a multidisciplinary approach, as these conditions require.

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Effectiveness of Immune Checkpoint Inhibitors in Transplant Recipients with Progressive Multifocal Leukoencephalopathy

Cited by 24 publications

References 5 publications

On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19

On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19

Novel treatments for progressive multifocal leukoencephalopathy

Immunosuppression-related neurological disorders in kidney transplantation

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