Polyomavirus-Specific T Cells in Progressive Multifocal Leukoencephalopathy: A Multicenter Retrospective Analysis

Area of Science:

• Immunology
• Neurology
• Oncology

Background:

• Progressive multifocal leukoencephalopathy (PML) is a rare, life-threatening brain infection caused by JC polyomavirus (JCPyV).
• Currently, no effective antiviral therapies exist for PML, necessitating novel treatment strategies.
• Cellular therapies, specifically polyomavirus-specific T cells (PyVST), have emerged as a potential therapeutic option.

Purpose of the Study:

• To evaluate the real-world effectiveness and safety of PyVST in patients diagnosed with PML.
• To identify factors influencing treatment outcomes in PML patients receiving PyVST.

Main Methods:

• Retrospective analysis of 64 PML patients from 13 centers who received PyVST alongside standard care.
• Evaluation of patient characteristics, T-cell product details, and clinical outcomes, including survival and adverse events.
• Multivariate analysis to identify predictors of survival.

Main Results:

• Hematologic malignancies were the most common predisposing condition (51.6%).
• One-year survival rate was 62% (excluding non-PML deaths).
• Lower CSF JCPyV DNA levels at therapy initiation were significantly associated with improved survival (p=0.0266).
• PyVST demonstrated a favorable safety profile with rare adverse events like IRIS (7.8%).

Conclusions:

• Adoptive T cell therapy using PyVST offers encouraging one-year survival rates for PML patients.
• PyVST exhibits a favorable safety profile, with low incidence of adverse events.
• Further research is needed to optimize T-cell generation strategies and identify patient/product characteristics influencing outcomes.