What is a cytokine storm?

Several different cancer treatments can cause cytokine storms, including immunotherapies like CAR T cell therapy and bispecific antibodies, and targeted therapies like menin inhibitors.

But what is a cytokine storm, and is it the same thing as cytokine release syndrome? How serious is it, and which patients are most likely to develop this potential side effect?

Read on, to learn the answers to these and other questions.

What is a cytokine storm?

A cytokine storm is a potentially life-threatening condition that occurs when the immune system releases too many cytokines all at once. It causes a severe inflammatory reaction in your body.

The release of cytokines is part of your body’s normal defense system. When that process gets out of control, it’s called a cytokine storm.

What is a cytokine?

Cytokines are natural proteins secreted by various cells, including a type of immune cell called a T cell. They act as a stimulant to fire up the immune system. It’s why you develop a fever when you get an infection, and why your hand or leg swells up when you get an injury there.

Is a cytokine storm the same thing as cytokine release syndrome?

Yes and no. Cytokine storms can have several different causes, including a severe infection. Cytokine release syndrome is just the term we typically use when a storm is directly related to a patient receiving certain cancer therapies. So, cytokine release syndrome is a subtype of cytokine storms.

What are the first signs of a cytokine storm?

Early signs of a cytokine storm include:

• Body aches
• Chills
• Fatigue
• Fever

But these can also be symptoms of the flu, a cold, or some other type of infection. So, they are not specific to cytokine storms.

Later symptoms can include sudden changes in blood pressure (either high or low) and a drop in blood-oxygen levels (hypoxia).

Are there any symptoms that are specific to cytokine storms?

No. That’s why physicians must act based on whatever they see. We don’t want to administer certain drugs too soon, because they can mask a fever. So, we have to rule out an infection first. Usually, we can tell within 24 hours if it’s that or something else.

What triggers cytokine storms?

Here at UT MD Anderson, they’re usually a side effect of cancer treatment. Cytokine storms are pretty common with CAR T cell therapy, and to a lesser extent, with bispecific antibodies and menin inhibitors.

But cytokine storms can also sometimes be caused by systemic infections, like COVID-19, if the body responds too strongly to a threat.

Which patients are most likely to experience cytokine storms?

Anyone who receives one of the therapies mentioned above could potentially develop one. Currently, they are used to treat certain types of leukemia and lymphoma, so patients with one of those diseases are probably the most at risk.

How are cytokine storms typically treated?

With cancer patients, there are three options.

• Pausing therapy: We’ll stop whatever therapy you’re on until the symptoms subside and then carefully reintroduce it.
• Steroids: We’ll administer steroids, which can help calm your immune system down.
• Anti-cytokine drugs: We’ll administer anti-cytokine drugs, which can reverse your symptoms fairly quickly.

How serious are cytokine storms?

If left untreated, cytokine storms can be fatal, but they’re manageable in almost every case.

We’ve learned a lot about this side effect since some of the drugs that cause them first came out. And, one of the things we’ve noticed is that if someone has what’s called a high tumor burden — or a lot of cancer in their system — the storms tend to be pretty dramatic. So, if we can reduce your tumor burden first, the storm will be less impressive.

Similarly, cytokine storms often happen because a lot of cells are being stimulated at once. So, if we can either shorten the duration of that reaction, or control it so that it happens to a lesser degree over a longer period of time, you will not have the storm.

We’re still coming up with new strategies to manage this side effect, with drugs that only bind for a very short time to the target and don’t give a big stimulation right at the beginning. So, cytokine storms are becoming less of an issue for our patients.

Elias Jabbour, M.D., is a leukemia specialist with a particular interest in acute lymphocytic leukemia.

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