Immune effector cell-associated neurotoxicity syndrome (ICANS) is a possible side effect of certain immunotherapies. This condition causes inflammation in the brain, leading to symptoms.
ICANS is a result of the body’s reaction to certain cancer treatments. This reaction does not happen to everyone who receives those treatments, but it is important to recognize the symptoms.
The symptoms of ICANS can range from mild to severe and can affect abilities such as speech, movement, and thinking. ICANS is
This article discusses further details of what ICANS is, its symptoms, its causes, and how doctors diagnose and treat it.
ICANS is a reaction to certain immunotherapy treatments for cancer, such as chimeric antigen receptor (CAR) T-cell therapy and bispecific T-cell engager (BiTE) therapy. ICANS occurs in an estimated
The symptoms of ICANS can vary from person to person. Many people experience only mild symptoms, which can make the condition more difficult to recognize.
The possible symptoms include:
- headache
- difficulty concentrating
- lethargy
- agitation
- hallucinations
- tremors
- difficulty speaking, reading, writing, or understanding language (aphasia)
- confusion
- memory loss
- personality changes
An estimated
- seizures or status epilepticus
- brain swelling
- brain bleed (hemorrhage)
On average, ICANS develops 5 days after a CAR T-cell therapy infusion, but in some cases it can appear more than 3 weeks afterward.
Experts do not fully understand why ICANS happens, but it may be due to an increase in cytokines, which are substances that cause inflammation.
Cytokines are part of the body’s immune response. Immunotherapies such as CAR T-cell therapy provoke the immune response, helping the immune system target and attack cancer cells. In the process, these treatments stimulate inflammation.
The increase in inflammation may affect the brain, causing a breakdown of the layer of cells that control what can pass from blood vessels into the brain.
When this barrier breaks down, certain cells that can cause further inflammation and toxicity can enter the brain. This can affect the way the brain and central nervous system work, leading to symptoms.
Possible risk factors for ICANS include:
- cytokine release syndrome
- preexisting neurologic dysfunction
- a high volume of cancer in the body
- high levels of lactate dehydrogenase
While a person is receiving immunotherapies that can cause ICANS, particularly CAR T-cell therapy, a healthcare professional will assess the person
As part of this assessment, the healthcare professional may ask the person questions, perform a neurological examination, or order blood tests.
Healthcare professionals use a grading system called the immune effector cell-associated encephalopathy (ICE) score, which ranges from 1 through 4, to describe the extent of a person’s ICANS symptoms. This grading scale also helps them determine what treatment or monitoring a person may need.
The grading scale is as follows:
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | |
|---|---|---|---|---|
| ICE score | 7 to 9 | 3 to 6 | 0 to 2 | 0 |
| Level of consciousness | wakes up without prompt | wakes up to a voice | wakes up to a touch | difficult or unable to wake up (coma) |
| Seizure | — | — | seizures lasting less than 5 minutes | seizures lasting more than 5 minutes |
| Motor findings | — | — | — | weak or unable to move on one or both sides of the body |
| Elevated ICP/cerebral edema | — | — | localized swelling in the brain that is visible on imaging | • widespread brain swelling • abnormal posturing • signs of increased pressure in the brain |
Treatment for ICANS depends on the severity of the condition.
For people with grade 2 or higher, a doctor may prescribe medications that help reduce inflammation, such as corticosteroids, until the symptoms improve.
If a person has severe symptoms, doctors may use levetiracetam for seizures or benzodiazepines for status epilepticus. A more experimental approach to managing ICANS is adjusting the potency of the immunotherapy itself.
If a person’s symptoms do not improve with treatment, a doctor may treat ICANS with chemotherapy that targets the T cells in the body to stop the inflammatory immune response.
In rare and extreme cases, a person may die as a result of ICANS or may experience long-term complications. However, in most cases, people recover without any lasting damage.
Below are some answers to frequently asked questions about ICANS.
What is the difference between ICE and ICANS?
ICE is the grading system that healthcare professionals use to determine the severity of ICANS.
What is the mortality rate of ICANS?
It is difficult to determine a mortality rate for ICANS. A
Is ICANS reversible?
Yes. Most people who have ICANS fully recover from the condition and do not experience long-term complications.
How long does it take for ICANS symptoms to show?
On average, the symptoms of ICANS begin around
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a condition that results from the body’s reaction to certain immunotherapy treatments for cancer.
These treatments stimulate the immune system, causing an increase in inflammation. If this inflammation affects the brain, it may cause symptoms.
Not everyone who receives immunotherapy treatment gets ICANS, and most people who develop the condition have only mild symptoms. However, a healthcare professional will frequently monitor a person who is undergoing immunotherapy treatment such as CAR T-cell therapy to make sure they get prompt care if they begin showing signs.
In most cases, people fully recover from ICANS. However, if a person begins to experience symptoms such as difficulty thinking or talking, confusion, or headaches, they should tell their doctor right away.