[Column] Another Face of immunotherapy: immune-related adverse events

"Doctor, my hair is suddenly falling out. Didn't you say this anti-cancer drug wouldn't cause hair loss?"

Ms. Jang, a 51-year-old female patient, was diagnosed with cancer of unknown primary origin a year ago, presumed to be lung cancer. She had undergone multiple rounds of cytotoxic anticancer treatment but showed no response. However, after receiving atezolizumab—recently covered by insurance—as a third-line therapy, her condition dramatically improved. She was continuing treatment with no apparent side effects, but then developed alopecia areata, a condition she had previously only read about in the literature as a rare immunotherapy-related event.

While immuno-oncology drugs can deliver remarkable results, they may also trigger unexpected immune-related adverse events (IrAEs) that attack the body's normal tissues and organs.

Immune checkpoint inhibitors, commonly referred to as immunotherapies, act like a switch on the immune system, helping immune cells better recognize and attack cancer cells. Patients are often told that these drugs enhance their immunity against cancer. However, once switched on, the immune system may also mistakenly attack the body itself. This is known as an immune-related adverse event (IrAE). IrAEs differ from traditional chemotherapy side effects in both presentation and scope, often affecting multiple organs. As immunotherapy indications expand, the importance of recognizing and managing IrAEs has grown significantly.

What are the side effects?

Immune checkpoint inhibitors generally have fewer side effects than traditional anticancer drugs (cytotoxic and targeted), making them relatively safe. However, IrAEs can sometimes lead to serious complications. Between 16 percent and 24 percent of patients receiving immune checkpoint inhibitors report fatigue, though it is rarely as severe as that seen with cytotoxic drugs. Hypersensitivity reactions related to administration may also occur, but these are typically mild and well managed.

More problematic IrAEs can affect the entire body and most commonly appear within the first three to six months of treatment. Skin reactions are typically seen within the first four to five weeks, while gastrointestinal and pulmonary side effects tend to occur after five to six weeks. Depending on the treatment regimen and individual factors, atypical presentations can also arise months later. Serious, life-threatening IrAEs are reported in approximately 0.3 to 1.3 percent of patients. Although this is a lower frequency compared to conventional therapies, conditions such as enteritis, pneumonitis, and myocarditis pose significant risks and require close attention.

How are side effects treated? Can treatment resume?

IrAEs are classified by severity, and treatment approaches vary depending on the organs involved. In grade 1 IrAEs, which are asymptomatic or mildly symptomatic, treatment may continue with close monitoring for worsening symptoms. For grade 2 IrAEs—moderate symptoms—immune checkpoint inhibitors are discontinued, and low-dose steroids may be administered.

In the case of grade 3 or 4 IrAEs, which involve severe or life-threatening symptoms, the immune checkpoint inhibitor is immediately stopped. High-dose steroids are used, and additional immunosuppressants may be considered based on symptom severity and response. Most IrAEs can be effectively managed if detected and treated early, underscoring the importance of vigilance during treatment.

The decision to resume immunotherapy after an IrAE is made carefully by both the patient and healthcare team, taking multiple factors into account. While many patients are able to restart treatment successfully, re-treatment is not recommended if the initial side effect was severe or remains uncontrolled.

Important reminders for patients

Immunotherapy, particularly immune checkpoint inhibitors, offers new hope in the fight against cancer. However, even this promising approach is not without risks. Characteristic and sometimes serious side effects can occur. Fortunately, most IrAEs are manageable if caught early and treated appropriately.

If you experience unusual symptoms after treatment—such as persistent fatigue, unexplained diarrhea, shortness of breath, or coughing—it is crucial to inform your healthcare provider. Recognizing and responding to adverse events is just as important as achieving treatment success. If you notice any changes in your condition during therapy, do not hesitate to reach out to your care team. That could be the key to successful immunotherapy.