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Preexisting virus-specific T cells in patients with progressive multifocal leukoencephalopathy (PML) correlate with improved outcomes when treated with immune checkpoint inhibitors (ICIs). This suggests that antiviral immunity is crucial for effective ICI therapy in PML.

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Area of Science:

  • Immunology
  • Neurology
  • Oncology

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease caused by JC virus (JCV) reactivation in immunocompromised individuals.
  • Immune checkpoint inhibitors (ICIs) offer therapeutic potential for PML, but treatment responses are variable, and predictive biomarkers are needed.

Purpose of the Study:

  • To investigate the association between pretreatment JC virus (JCV)- and/or BK virus-specific T cells and the efficacy of ICI treatment in PML patients.
  • To identify potential biomarkers for predicting treatment response and outcomes in PML.

Main Methods:

  • A retrospective cohort study involving 111 patients with PML treated with ICIs (pembrolizumab, nivolumab, or atezolizumab).
  • Patients were stratified based on the presence of peripheral virus-specific T cells (detected via ELISpot/flow cytometry) before treatment.
  • Clinical outcomes, viral load, and immune-related adverse events were compared between T cell-positive, T cell-negative, and unknown T cell status groups.

Main Results:

  • Patients with detectable virus-specific T cells prior to ICI therapy demonstrated significantly higher response rates (86% vs. 23% for T cell-negative; P < .001).
  • T cell-positive patients exhibited improved survival (P = .002) and better functional outcomes (modified Rankin Scale score, P = .009) compared to T cell-negative patients.
  • Lower JC viral loads in cerebrospinal fluid (P = .01) and fewer immune-related adverse events (P = .02) were observed in T cell-positive patients.

Conclusions:

  • Preexisting functional virus-specific T cells are associated with enhanced clinical response, prolonged survival, and reduced toxicity in PML patients undergoing ICI therapy.
  • The presence of antiviral immunity prior to treatment may be a critical factor for successful ICI therapy in PML.
  • These findings highlight the potential of virus-specific T cell monitoring as a predictive biomarker for ICI treatment in PML.