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Diagnosis and management of ICANS

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Topics: Advanced therapy medicinal productsCautions and contraindicationsGuidancePrescribing

Guidance on the management of immune effector cell-associated neurotoxicity syndrome (ICANS) in adults receiving licensed CAR-T cell products.

This article forms part of a series
  1. Understanding acute CAR-T cell therapy toxicities in adults
    1. Diagnosis and management of cytokine release syndrome (CRS)
    2. Diagnosis and management of ICANS
    3. Medications for treating CRS and ICANS

Contents

  1. Recognition and differential diagnosis
  2. Monitoring
  3. Management
    1. ICANS treatment algorithm
    2. Alternative description of the ICANS treatment algorithm image
    3. Management table for the treatment of ICANS

Recognition and differential diagnosis

ICANS can present as:

  • delirium
  • delirium
  • encephalopathy
  • aphasia
  • lethargy
  • difficulty concentrating
  • agitation
  • tremor
  • seizures
  • rarely cerebral oedema
  • headache
  • changes in handwriting

ICANS normally lasts between 2 to 4 days but can persist for weeks.

The onset of neurotoxicity can coincide with CRS but can also occur as late as the third or fourth week following CAR-T cell therapy infusion, after CRS resolves.

Consider alternative causes of neurological dysfunction such as:

  • infection
  • opioid toxicity
  • haemorrhage
  • drugs
  • electrolyte imbalance
  • metabolic acidosis

Monitoring

Regularly monitor for signs and symptoms of ICANS in CAR-T cell therapy in line with the individual product SmPC, and national service specification.

Measure the immune effector cell-associated encephalopathy (ICE) score to assess for encephalopathy twice a day or more frequently if ICANS is suspected.

Management

The grade of ICANS indicates the management and treatment plan. See Understanding acute CAR-T cell therapy toxicities in adults (SPS page) for more information on how ICANS is graded.

ICANS management includes corticosteroids. In severe and refractory cases, off-label treatments such as anakinra may be used in line with Trust formulary processes.

Input from a neurologist and early transfer to ICU for monitoring is recommended.

Treat seizures with advice from the neurology team or in line with local guidelines. Consider seizure prophylaxis with non-sedating anti-seizure medication for patients with an increased risk of ICANS.

Management of ICANS should be rapidly escalated through the treatment algorithm if there is a lack of clinical response.

ICANS treatment algorithm

The figure below outlines the ICANS treatment algorithm.

The flowchart illustrates 4 steps in the treatment algorithm:

Step 1

  • Every patient should have a baseline ICE assessment
  • Baseline CT or MRI brain is recommended

Step 2

  • If ICANS is suspected, immediately contact the CAR-T team
  • Management should be guided by the CAR-T consultant in conjunction with a neurologist
  • If concurrent CRS also follow the CRS management algorithm

Step 3

  • If ICANs is suspected a thorough neurological examination should be performed.  The following investigations should be performed: EEG; MRI or CT brain; frequent monitoring for cognitive function for example handwriting tests; three times daily ICE assessment; consider diagnostic lumbar puncture
  • Alternative causes of neurological dysfunction such as infection, opioid toxicity, haemorrhage, drugs, electrolyte imbalance or metabolic acidosis should be considered and treated

Step 4

  • Patients must be monitored closely and treatment rapidly escalated if there is lack of clinical response or further deterioration
  • CAR-T toxicity treatment decisions should be undertaken by the attending consultant or CAR-T team and escalation plan pre-empted where possible to support rapid treatment escalation when required.
  • If part of a clinical trial, contact the trial team and follow the specific trial protocol for management of ICANS

Management table for the treatment of ICANS

 

ICANS treatment algorithm and management table

A printable version of the ICANS treatment algorithm and management table.