Combined Treatment With Pembrolizumab and Allogenic BK Virus-Specific T Cells in Progressive Multifocal Leukoencephalopathy: A Case Report. 2021

Rebecca Wicklein, and Simon Heidegger, and Mareike Verbeek, and Britta Eiz-Vesper, and Britta Maecker-Kolhoff, and Jan Stefan Kirschke, and Agata Page, and Thomas Korn, and Bernhard Hemmer, and Marcus Deschauer
From the Department of Neurology (R.W., T.K., B.H., M.D.), Klinikum rechts der Isar, Technical University Munich; Medical Department III for Hematology and Oncology (S.H., M.V.), Klinikum rechts der Isar, Technical University Munich; Institute for Transfusion Medicine (B.E.-V.), Hannover Medical School; Department of Pediatric Hematology and Oncology (B.M.-K.), Hannover Medical School; Department of Neuroradiology (J.S.K.), Klinikum Rechts der Isar, Technical University Munich; Unilabs A/S (A.P.), Copenhagen, Denmark; Institute of Experimental Neuroimmunology (T.K.), Klinikum rechts der Isar, Technical University of Munich; and Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany. rebecca.wicklein@tum.de.

We report a combination of BK virus-specific T cells and pembrolizumab as a treatment option in progressive multifocal leukoencephalopathy (PML). A 57-year-old male patient diagnosed with PML presented a fast-progressing right hemiparesis, aphasia, and cognitive deficits. Brain MRI showed a severe leukoencephalopathy with diffusion restriction. The patient was treated with 10 doses of pembrolizumab (2 mg/kg body weight) in differing intervals and 2 partially human leukocyte antigen-matched allogenic BK virus-specific T cell transfusions after the fifth pembrolizumab treatment. Although pembrolizumab alone decreased the viral load but failed to control the virus, BK-specific T cell transfer further enhanced the decline of JC virus copies in the CSF. Moreover, the regression of leukoencephalopathy and disappearance of diffusion restriction in subsequent brain MRI were observed. The combined treatment resulted in a clinical stabilization with improvements of the cognitive and speech deficits. This case supports the hypothesis that pembrolizumab is more efficient in the presence of an appropriate number of functional antigen-specific T cells. Thus, the combined treatment of pembrolizumab and virus-specific T cells should be further evaluated as a treatment option for PML in future clinical trials.

UI MeSH Term Description Entries
D007968 Leukoencephalopathy, Progressive Multifocal An opportunistic viral infection of the central nervous system associated with conditions that impair cell-mediated immunity (e.g., ACQUIRED IMMUNODEFICIENCY SYNDROME and other IMMUNOLOGIC DEFICIENCY SYNDROMES; HEMATOLOGIC NEOPLASMS; IMMUNOSUPPRESSION; and COLLAGEN DISEASES). The causative organism is JC Polyomavirus (JC VIRUS) which primarily affects oligodendrocytes, resulting in multiple areas of demyelination. Clinical manifestations include DEMENTIA; ATAXIA; visual disturbances; and other focal neurologic deficits, generally progressing to a vegetative state within 6 months. (From Joynt, Clinical Neurology, 1996, Ch26, pp36-7) Encephalitis, JC Polyomavirus,Progressive Multifocal Leukoencephalopathy,JC Polyomavirus Encephalopathy,Encephalopathies, JC Polyomavirus,Encephalopathy, JC Polyomavirus,JC Polyomavirus Encephalitis,Leukoencephalopathies, Progressive Multifocal,Multifocal Leukoencephalopathies, Progressive,Multifocal Leukoencephalopathy, Progressive,Progressive Multifocal Leukoencephalopathies
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D001739 BK Virus A species of POLYOMAVIRUS apparently infecting over 90% of children but not clearly associated with any clinical illness in childhood. The virus remains latent in the body throughout life and can be reactivated under certain circumstances. BK polyomavirus,Human Polyomavirus BK,Polyomavirus, BK,Polyomavirus hominis 1,Polyomavirus BK, Human
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D016896 Treatment Outcome Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series. Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes
D061067 Antibodies, Monoclonal, Humanized Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab. Antibodies, Humanized,Humanized Antibodies
D019562 Viral Load The quantity of measurable virus in a body fluid. Change in viral load, measured in plasma, is sometimes used as a SURROGATE MARKER in disease progression. Viral Burden,Virus Titer,Burden, Viral,Load, Viral,Titer, Virus

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