Immune-Related Adverse Events: How to Recognize and Manage irAEs in Cancer Patients

What Are Immune-Related Adverse Events?

When cancer patients receive immune checkpoint inhibitors (ICIs), their immune system gets a powerful boost to attack tumors. But sometimes, that same immune response turns on healthy tissues-causing inflammation and damage. These unintended side effects are called immune-related adverse events, or irAEs. Unlike traditional chemo side effects like nausea or hair loss, irAEs mimic autoimmune diseases. They can show up in almost any organ: the gut, lungs, skin, thyroid, liver, even the heart or brain.

irAEs weren’t widely understood until after 2011, when the first ICI drug, ipilimumab, was approved for melanoma. Since then, as more cancers are treated with these drugs-like pembrolizumab and nivolumab-the number of patients experiencing irAEs has climbed. About 83% of people on CTLA-4 inhibitors, 72% on PD-1 inhibitors, and 60% on PD-L1 inhibitors will have at least one irAE. Some come early, within weeks. Others show up months after treatment ends. That’s why you can’t just stop monitoring after the last infusion.

Which irAEs Are Most Common?

Not all irAEs are created equal. Some are mild and common. Others are rare but deadly.

• Gastrointestinal: Diarrhea and colitis are the most frequent. About 1 in 5 patients on ICIs develop this. It starts with loose stools, then can turn bloody and severe.
• Endocrine: Thyroid problems (like hypothyroidism) are very common-up to 20% of patients. Less common but serious is hypophysitis, where the pituitary gland gets inflamed, messing up hormone production.
• Dermatologic: Rashes, itching, and blistering skin reactions happen in up to 30% of patients. Often, it’s just a mild rash, but sometimes it spreads fast.
• Pulmonary: Pneumonitis (lung inflammation) is less common but dangerous. Symptoms like dry cough, shortness of breath, or fever need urgent evaluation.
• Hepatic: Liver toxicity shows up as elevated liver enzymes. It’s often silent until blood tests reveal it.
• Neurological: Nerve and brain involvement is rare-under 1%-but can be fatal. Think muscle weakness, confusion, seizures, or numbness.
• Cardiac: Myocarditis is rare (less than 1%) but has a 2.7% death rate among those affected. Chest pain, palpitations, or sudden fatigue are red flags.

What makes irAEs tricky is that they don’t always look like classic autoimmune diseases. A rash from an irAE might not itch like eczema. Thyroid problems might come on so slowly that patients think they’re just tired from cancer. That’s why patients and doctors need to be hyper-aware.

How Are irAEs Graded and Diagnosed?

Doctors don’t guess. They use a strict system called the Common Terminology Criteria for Adverse Events (CTCAE). It has four grades:

• Grade 1: Mild symptoms. No treatment needed. Just monitor.
• Grade 2: Moderate symptoms. Interferes with daily life. Stop ICI. Start corticosteroids.
• Grade 3: Severe. Hospitalization needed. Stop ICI. High-dose steroids.
• Grade 4: Life-threatening. Emergency care. ICU-level intervention.

Before treating an irAE, doctors must rule out other causes. Is that diarrhea from an infection? Is the liver enzyme rise from a different drug? Is the low platelet count from cancer spreading to bone marrow? You can’t assume it’s an irAE. Blood tests, imaging, biopsies, and sometimes endoscopies are needed to confirm.

How Are irAEs Treated?

First-line treatment is almost always corticosteroids. But the dose and route depend on severity.

For Grade 2 irAEs, patients get oral prednisolone at 1 mg per kg of body weight per day. For example, a 70 kg person gets 70 mg daily. Treatment continues until symptoms drop to Grade 1 or less. Then, the steroid is slowly tapered over 4 to 6 weeks. Rushing this step causes rebound inflammation.

For Grade 3 or 4, steroids go intravenously. Methylprednisolone at 1-2 mg/kg/day (up to 1,000 mg/day) is given for 3 days, then switched to high-dose oral prednisolone. This is done in a hospital. If there’s no improvement after 48 hours, it’s called steroid-refractory-and you need stronger drugs.

Second-line options include:

• Infliximab: A TNF-alpha blocker. Used for colitis, pneumonitis, and some skin reactions.
• Mycophenolate mofetil: For liver or kidney involvement.
• IVIG: For neurological or hematologic irAEs.
• Vedolizumab: Newer option for colitis that doesn’t respond to steroids or infliximab. It targets the gut only, so fewer side effects.
• Cyclophosphamide: Reserved for severe, life-threatening cases like myocarditis.

Importantly, treating irAEs doesn’t kill the cancer-fighting effect of ICIs. Studies show tumor control stays strong even after using these immunosuppressants. That’s a big relief for oncologists and patients.

What About Hormone Problems?

Endocrine irAEs are different. You don’t suppress the immune system-you replace what’s broken.

If the thyroid stops working, you give levothyroxine. If the pituitary gland is damaged, you replace cortisol, thyroid hormone, sex hormones, or even vasopressin. These aren’t temporary fixes. Most patients need lifelong hormone therapy. Missing a dose can be dangerous. That’s why endocrinologists must be involved early.

One key point: never start steroids for suspected hypothyroidism without checking cortisol levels first. If the pituitary is down, giving thyroid hormone alone can trigger adrenal crisis. Always test cortisol before treating thyroid issues in ICI patients.

Why Timing and Communication Matter

irAEs don’t follow a schedule. They can appear after 6 months. Or after treatment ends. That’s why patients need to know: any new symptom, no matter how small, could be an irAE.

Patients often delay reporting. They think it’s just stress, fatigue, or aging. But early action saves lives. A 2023 analysis of 12,500 patients showed that if treatment starts within 48 hours of symptom onset, hospitalization rates drop from 34% to 19%.

Oncology nurses report that 79% of patients don’t understand the urgency. They wait too long. That’s why education isn’t optional-it’s critical. Patients need written materials, clear phone numbers, and a direct line to their care team after hours.

What Does Good Care Look Like?

Managing irAEs isn’t just about giving steroids. It’s about systems.

Leading cancer centers have dedicated immune toxicity teams. They include oncologists, endocrinologists, gastroenterologists, pulmonologists, neurologists, pharmacists, and nurses-all trained in irAEs. They meet weekly. They have protocols. They know who to call at 2 a.m.

Community clinics without these teams have higher complication rates. One study showed that after implementing formal protocols, severe irAE complications dropped by 37% in just 18 months.

Electronic health records now help too. Epic Systems updated its oncology module in 2023 to flag potential Grade 2+ irAEs automatically. If a patient reports diarrhea or rash in a portal, the system nudges the care team to act. That kind of tech saves time-and lives.

What’s on the Horizon?

The future of irAE management is about prediction and precision.

Researchers are looking for biomarkers. One 2023 study found that if a patient’s blood has IL-17 levels above 5.2 pg/mL before starting ICI, they’re 4.7 times more likely to develop a severe irAE. That could one day let doctors choose safer treatments for high-risk patients.

New drugs are being tested. Vedolizumab is already showing promise for colitis. Trials are comparing it to infliximab. Others are testing JAK inhibitors and other targeted agents.

And patient education is getting a global push. The European Society for Medical Oncology is creating multilingual materials in 15 languages. Because right now, 41% of patients say they don’t understand what symptoms to watch for.

What Should Patients Do?

If you’re on an immune checkpoint inhibitor:

• Know the warning signs: diarrhea, rash, shortness of breath, fatigue, confusion, chest pain, swelling, or unusual headaches.
• Report any new symptom immediately-even if it seems minor.
• Don’t stop your meds unless your doctor tells you to.
• Keep all follow-up blood tests and appointments.
• Ask for a copy of your irAE care plan. Know who to call after hours.
• Understand that steroid side effects (weight gain, insomnia, mood swings) are temporary. They’re the price of keeping you alive.

Most irAEs are reversible. About 85-90% of patients recover fully with proper care. But the window to act is small. Delay = danger.

Final Thoughts

Immune checkpoint inhibitors changed cancer care. But with great power comes great responsibility. irAEs are the flip side of that breakthrough. They’re not rare. They’re predictable. And they’re manageable-if you know what to look for and act fast.

The goal isn’t just to treat cancer. It’s to treat the whole person. That means watching for the hidden side effects, listening to patients, and having the right team ready. Because in cancer care, the best treatment isn’t always the most powerful drug. Sometimes, it’s the most attentive care.