Treatment-related progressive multifocal leukoencephalopathy: current understanding and future steps

Area of Science:

• Neuroscience
• Virology
• Immunology

Background:

• Progressive multifocal leukoencephalopathy (PML) is a rare, severe demyelinating disease of the brain.
• PML is caused by the JC polyomavirus and typically occurs in immunocompromised individuals.
• Acquired immune deficiency syndrome (AIDS) has historically been the most common predisposing condition for PML.

Purpose of the Study:

• To review the risks of PML associated with various pharmacological agents.
• To explore the proposed pathogenesis of PML development in relation to these drugs.
• To discuss potential strategies for mitigating PML risk in patients using these therapies.

Main Methods:

• Literature review focusing on PML and pharmacological agents.
• Categorization of therapies based on their unique, increased, or potential risk for PML.
• Analysis of the latent interval and prevalence associated with different drug classes.

Main Results:

• Pharmacological agents are increasingly recognized as a cause of PML.
• Therapies are categorized into those uniquely increasing risk (e.g., natalizumab), those increasing risk in predisposed individuals (e.g., rituximab), and those with potential risk.
• Unique risk-increasing agents show higher prevalence and a distinct latent interval before PML onset.

Conclusions:

• Certain pharmacological therapies, particularly monoclonal antibodies, significantly elevate the risk of developing PML.
• Understanding drug-specific PML risks and pathogenesis is crucial for patient management.
• Risk mitigation strategies are essential for preventing and managing PML in patients undergoing immunosuppressive therapies.