Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors

Abstract

Objective: Our aim was to assess the real-world effectiveness of immune checkpoint inhibitors for treatment of patients with progressive multifocal leukoencephalopathy (PML). Methods: We conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add-on to standard of care. Oneyear follow-up data were analyzed to determine clinical outcomes and safety profile. Logistic regression was used to identify variables associated with 1-year survival. Results: Predisposing conditions included hematological malignancy (n = 38, 48.1%), primary immunodeficiency (n = 14, 17.7%), human immunodeficiency virus/acquired immunodeficiency syndrome (n = 12, 15.2%), inflammatory disease (n = 8, 10.1%), neoplasm (n = 5, 6.3%), and transplantation (n = 2, 2.5%). Pembrolizumab was most commonly used (n = 53, 67.1%). One-year survival was 51.9% (41/79). PML-immune reconstitution inflammatory syndrome (IRIS)

Progressive Multifocal Leukoencephalopathy in a Chemotherapy-Naive Patient With Chronic Lymphocytic Leukemia: A Case Report

“…Although the survival rate of PML has improved drastically, especially in HIV patients, the mortality rate continues to be elevated when a rapid reversal of immune deficiency is not possible, which occurs in patients with hematologic malignancies [6,8,10]. Immune checkpoint inhibitors that target programmed cell death pathways, such as pembrolizumab and nivolumab, are promising treatment options as they upregulate T-cell activation and cell-mediated immune response [8][9][10]. Moreover, they seem to reduce the JC viral load, leading to disease stabilization and symptom improvement [14].…”

“…The initial asymptomatic infection usually occurs in childhood [ 2 ]. It is followed by a latent/persistent infection of the kidneys, as well as hematopoietic organs, where it undergoes reactivation and transformation into a neurotropic virus, enabling the invasion of the nervous system and replication in the glial cells, ultimately causing multifocal demyelination [ 2 , 7 - 8 ]. Given the multifocal involvement, the classical clinical presentation is characterized by progressively worsening multifocal neurologic symptoms, which depend on the localization of the lesions and can present with motor and sensory deficits, ataxia, aphasia, visual changes, seizures, as well as cognitive and behavioral abnormalities, headache, vertigo, and parkinsonism [ 8 , 11 ].…”

“…Despite the inherent secondary immunosuppression in patients with CLL due to impaired humoral and cellular immunity [ 12 ], the significant risk factor for PML in hematologic patients is immunosuppressive chemotherapy, radiotherapy, or hematopoietic stem cell transplant [ 7 , 13 ]. Nowadays, the disease is rarely described in patients not undergoing therapy [ 8 ].…”

“…However, its radiological appearance can be heterogeneous and depends on the underlying etiology [ 2 , 11 ]. Cerebrospinal fluid analysis and documentation of the virus are essential for the diagnosis, although a negative PCR for the JC virus in the cerebrospinal fluid does not exclude the diagnosis [ 8 ]. Our patient presented with a typical neuroradiological pattern, with biparietal intra-axial white substance lesions, hyperintense in T2 and hypointense in T1, more pronounced in the right hemisphere, with extension to the corpus callosum and the mesencephalon, and a discrete mass effect.…”

“…The diagnosis is based on clinical findings, typical neuroradiological findings, the presence of the JC virus in cerebrospinal fluid, or characteristic histopathologic findings on a biopsy of the central nervous system (CNS) [ 7 ]. The treatment is based on the immune system's reconstitution, as no specific antiviral therapy is available [ 8 ]. Treatment with checkpoint inhibitors has been applied recently [ 9 ] but has shown mixed outcomes in patients with hematologic malignancies [ 10 ].…”