Cytokine Storm

As cancer research progresses, there is new hope for longevity after diagnosis with cutting-edge treatments like immunotherapy. This treatment has emerged as a key player in cancer therapy by helping your immune system fight cancer. Cancer cells tend to evade the effects of your normal immune system, but immunotherapy helps your immune system fight against those cells more effectively, per the National Cancer Institute.

However, as with most treatments, immunotherapy has its side effects. More specifically, experts are learning more about immune-related adverse events (irAEs) that may occur with immunotherapy — and that can have symptoms mirroring autoimmune disease.

It’s one part of learning what life looks like with cancer in a world where emerging cancer treatments extend longevity. “Cancer and oncology are seeing a huge paradigm shift, where we are getting closer to the idea of treating cancer like a chronic disease,” says Alexa Simon Meara, MD, Associate Professor of Internal Medicine at The Ohio State University Wexner Medical Center. “What survivorship means now is different.”

Here’s what you need to know about irAEs and how to advocate as a patient or caregiver.

What Are irAEs?

Immune-related adverse events are toxicities caused by the use of immune checkpoint inhibitors, which are a type of immunotherapy. Although they’re believed to be rare, experts now know that these side effects can persist in some patients even after immunotherapy has been paused, per a 2023 review in the Journal of ImmunoTherapy of Cancer.

That same review found that the most common immunotherapies used on patients who experienced irAEs were pembrolizumab (24 percent) and nivolumab (37 percent). Twenty percent of patients experienced rheumatological irAEs, while 19 percent experienced neurological, 16 percent gastrointestinal, and 14 percent dermatological irAEs.

The irAEs persisted for a median of 180 days, with more than half of patients experiencing chronic irAEs for over six months.

“Immunotherapy has been a real game changer for a lot of cancers and we’re very excited to use it, because it doesn’t have the same side effects as chemo,” says Pauline Funchain, MD, Associate Professor of Medicine at Stanford Medicine. “But the side effects are really from your own immune system.”

After immunotherapy, your own immune cells may cause inflammation in various parts of the body that lead to symptoms. For instance, if you have inflammation of the colon, that might become diarrhea or abdominal pain. If you have inflammation in the joints, that can cause heat and swelling.

“The side effects kind of look like rheumatoid arthritis or ulcerative colitis, but they’re not exactly the same and they don’t respond to drugs in exactly the same way,” adds Dr. Funchain. “It’s almost like we’re seeing a brand-new set of diseases we’ve never seen before.”

If you go through immunotherapy, it’s important to alert your doctor of any symptoms. Keep a log of what you experience and report when you notice something out of the ordinary.

Although doctors are still learning the best way to treat irAEs, they might recommend a high level of steroids to combat the effects. This course of treatment typically lasts for at least two months. You won’t be able to continue immunotherapy while you’re on steroids since they have opposite effects on the immune system.

A Real Patient Story

In April 2016, Regina Santamarina’s husband, Rodrigo, was diagnosed with advanced-stage cholangiocarcinoma (a rare bile duct cancer). While chemotherapy was the first line of treatment, both Regina and her husband knew it was not the full answer for his cancer, which had already caused metastasis in his lungs.

“We started researching clinical trials and found one for immunotherapy,” says Regina. “Shortly after the first dose, he started developing side effects. When the symptoms started, we would rush to our local hospital, but they didn’t know how to handle those reactions because he was severely ill.”

Rodrigo was immediately admitted to an intensive care unit and taken care of by whichever oncologist was on call, since there wasn’t an immunotherapy complications team at the time. He had inflammation in his lungs and heart. His liver function tests were also highly abnormal.

“They started giving him prednisone, which is a wonderful medication, but they had to use it in extraordinarily high doses,” says Regina. “When we tried tapering the prednisone down, another organ would flare up and the original organ would become even worse than it was in the beginning.”

Rodrigo ultimately experienced compression fractures in his spine as a result of the prednisone use. During that time, the tumor itself was shrinking, so the immunotherapy was working — but Regina notes they weren’t able to control the effects that the immunotherapy was causing on her husband’s healthy organs. Ultimately, the immunotherapy affected Rodrigo’s bone marrow and he became transfusion dependent.

“We decided that there was no point in fighting this anymore and that we were just going to focus on giving him comfort measures,” says Regina. “We accepted we were not going to win the battle.”

Rodrigo’s doctor had just started brainstorming how to assemble a team that went beyond oncology to also include a neurologist, hematologist, and other specialists to mitigate the effects of the immunotherapy when Rodrigo passed away in October of 2017.

How to Advocate as a Patient or Caregiver

Since Rodrigo’s passing, more awareness has been raised around these reactions. Regina’s advice to other patients: Don’t wait to get the help you need — and work with your doctor to create a team of specialists who can work to help you manage the symptoms, if possible.

“Some patients might not feel comfortable bringing up symptoms because they’re worried they’ll be taken off the immunotherapy, especially if it is part of a clinical trial,” says Regina. “Immunotherapy means hope, which is the most important gift that a family facing cancer can have. Just because you have one of the side effects today doesn’t mean that you’re not going to be able to continue receiving the treatment.”

Regina says that with the knowledge and research available on irAEs today, she has met patients who have gone through several side effects, received the appropriate treatment, and eventually became cancer-free (all while keeping their immune reactions under control).

More funding, research, and data collection are needed to more fully understand irAEs, but there are still many steps you can take as a patient or caregiver for the best outcomes. Talk to your oncologist about early signs of toxicities, such as joint pain and fatigue. This may involve discussing what “normal” feels like for you as a cancer patient.

“Awareness is important,” says Dr. Meara. “Ask your oncologist what subspecialists they’re working with to help with these toxicities.” Working with other specialists can also help you see your overall diagnosis and treatment course from a different perspective.

“It’s a unique emotional state to have cancer and to be living with it, and we just haven’t figured out how to deal with that as a culture yet,” says Dr. Meara. “That’s why the addition of having a third party, like a rheumatologist, is able to have these conversations very differently.”

Be a More Proactive Patient with PatientSpot

PatientSpot (formerly ArthritisPower) is an app and website made for people living with chronic conditions. You can track your symptoms and treatments, access support resources relevant to your needs, and choose to participate in research to help advance the understanding of chronic diseases. Learn more and sign up here.

Immunotherapy to Treat Cancer. National Cancer Institute. September 24, 2019.

Interview with Alexa Simon Meara, MD, associate professor of internal medicine at The Ohio State University Wexner Medical Center.

Chronic immune-related adverse events in patients with cancer receiving immune checkpoint inhibitors: a systematic review. Journal for ImmunoTherapy of Cancer. July 11, 2023. doi:

Interview with Pauline Funchain, MD, associate professor of medicine at Stanford Medicine.

Interview with Regina Santamarina, patient advocate.

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