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Immune Effector Cell-Associated Neurotoxicity Delayed Relapse After Chimeric Antigen Receptor T-Cell Therapy: A Case

Anna Favero¹, Sara Mohamed², Marta Lisa Battista³

¹Neurology Unit, Department of Medical, Surgical and Health Sciences, University of Trieste, Italy.

Neurology(R) Neuroimmunology & Neuroinflammation

|November 17, 2025

Summary

This case study details a rare late relapse of immune effector cell-associated neurotoxicity syndrome (ICANS) after CAR T-cell therapy. It suggests ICANS may have a biphasic course, requiring extended patient monitoring.

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Area of Science:

Oncology
Immunology
Neuroscience

Background:

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a known complication of CAR T-cell therapy.
ICANS typically presents with a variable onset and is often considered a monophasic condition.

Purpose of the Study:

To report an exceptionally rare case of late-onset ICANS relapse following CAR T-cell therapy.
To highlight the diagnostic and management challenges associated with recurrent ICANS.

Main Methods:

A patient undergoing CAR T-cell therapy for large B-cell lymphoma was closely monitored for neurotoxicity.
Clinical assessments, neuroimaging, and laboratory tests were utilized to track symptom progression and inform treatment decisions.

Main Results:

The patient experienced a grade 4 ICANS episode with coma on day 14 post-infusion, requiring intensive care and treatment with methylprednisolone and anakinra, leading to recovery.
A subsequent grade 3 ICANS relapse occurred on day 40, presenting with disorientation, confabulation, and seizures, which resolved with levetiracetam, anakinra, and dexamethasone.

Conclusions:

This case underscores the possibility of delayed ICANS relapse beyond the conventional timeframe, emphasizing the need for prolonged patient surveillance.
The findings suggest a potential biphasic pattern of ICANS, necessitating further investigation into its underlying pathophysiology and optimal long-term management strategies.