Understanding Immunotherapy and Its Skin-Related Side Effects

Immunotherapy has transformed cancer treatment by helping the body’s immune system recognize and attack cancer cells more effectively.

According to Dr. Brittany Dulmage, an oncodermatologist at The Ohio State University Comprehensive Cancer Center, these therapies, known as immune checkpoint inhibitors, work by “releasing the brakes” on the immune system. Although this approach can be highly effective, it may also lead to side effects, particularly involving the skin, hair, and nails, as the immune system becomes more active.

CURE: Can you explain for patients what immune checkpoint inhibitors even are and how they work?

Dulmage: The immune system is designed to recognize "self" so that the immune system is not routinely attacking itself. One of the ways that the immune system recognizes the self is through different checkpoints. The checkpoints are essentially receptors, a molecule and a receptor on the surface of cells that interact with one another to tell the immune system, "I am part of you, leave me alone."

Immune checkpoint inhibitors disrupt that interaction. They take away the interaction between the immune system and the cancer cell to turn off the brakes, essentially, and allow the immune system to attack that cancer cell. In disrupting that checkpoint, they harness the power of the immune system itself to ultimately treat the target cancer cell.

Could you talk about some of the most common side effects patients should watch out for on their own.

Sure. Skin toxicity is the most common overall group of side effects. More than half of patients who get immunotherapy will develop some type of skin reaction. Of the skin toxicities, the most common is what's called a maculopapular or morbilliform eruption. Morbilliform means "measles-like"; it looks a lot like measles. It's red splotchiness that can be associated with some itch or discomfort. That type of skin reaction usually comes on early in the course of immunotherapy, within the first few cycles, and it is also typically self-limited, which means it will get better as immunotherapy goes on. It doesn't often require a ton of intervention on our side. We do treat it, but it is something that will improve over time.

That's very different from some of the other dermatologic toxicities, which can show up much later. We have some toxicities that show up after patients have been on treatment for months or even more than a year. Some of the more serious ones are blistering skin conditions where patients can develop frank blisters that can cause breakdown of the skin. A lot of associated itch or pain can leave patients at high risk for infection.

Itch is one we've talked a little bit about, which is quite common; about a third of patients who are exposed to immunotherapy will develop some degree of itch. It's usually not super severe, but it can be so severe that it interferes with daily activities or sleep.

To summarize: a measles-like rash is very common, itch is also quite common, and flares of chronic dermatologic conditions like eczema or psoriasis are risks. High-risk or worrisome would be the development of new blistering skin conditions.

How do you balance treatment benefits with potential risks?

I think that's a really important question. We don't want to use treatments that are going to suppress the immune system. The whole point of immunotherapy, as we discussed, is to rev up the immune system to let it do the work of targeting the cancer cell. If we use a medication that suppresses the immune system, we may lessen the effect of immunotherapy. A great example is steroids. A lot of dermatologic conditions will respond to oral steroids, but if we give a patient oral steroids, they may not be able to get their immunotherapy, or their immunotherapy may not be as effective.

I think one of the really big roles that we can play as dermatologists is that we can help pick a more targeted therapy for a patient's individual skin toxicity that isn't just high-dose steroids. I can say to the patient with eczema, "If your eczema is flaring, what is an eczema-specific medication I can give you that doesn't suppress your immune system as a whole?" It really just treats this narrow type of inflammation with eczema and, therefore, allows you to still get your immunotherapy at the appropriate dose.

We often ask: is the treatment compatible with immunotherapy? Can it be given alongside immunotherapy? What's tough is we don't always know the answer because a lot of the medications that become FDA-approved for dermatologic conditions are not studied in cancer patients during clinical trials. However, we can look at what that medicine is doing from an inflammation standpoint to try and pick things that are going to be the lowest risk to combine with immunotherapy.

My last question for you today: what should patients take away from our conversation today?

That's a great question. As far as immunotherapy is concerned, its introduction has drastically changed the way that cancer has been treated over the last 10 years. More and more types of malignancies are incorporating immunotherapy as part of their treatment approach. The number of patients who are receiving immunotherapy is going up every year as more types of cancer have indications to utilize it.

What that means as an oncodermatologist is that I am seeing more and more patients with side effects of immunotherapy. Things that maybe we thought were rare are being seen in much bigger quantities as the sheer number of patients has gone up. I think what patients can really do to advocate for themselves is to let their oncology teams know about changes from their baseline, about new side effects or new symptoms.

Hopefully, they can then be appropriately triaged early on and managed while they are lower-risk, lower-grade side effects. This ensures that immunotherapy can ultimately continue and does not need to undergo a treatment hold or necessitate steroids. Earlier engagement and sharing what they are experiencing that is new or different will allow it to be appropriately triaged earlier.

Transcript has been edited for clarity and conciseness.

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