Immune-related adverse events, monitoring, and when treatment is paused
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PD-1 inhibitor immunotherapy — cemiplimab or pembrolizumab — is the first-line systemic treatment for advanced cutaneous squamous cell carcinoma. Many people tolerate it well, and its side effects are different from those of chemotherapy: there is usually no hair loss, and nausea and low blood counts are uncommon.
The trade-off is a distinct set of problems called immune-related adverse events. This article explains what they are, the routine monitoring used to catch them early, how doctors decide whether to keep going, pause, or stop, why some effects need lifelong treatment while the drug continues, the special situation for transplant recipients, and the symptoms that mean you should call your team without waiting.
A PD-1 inhibitor works by taking a brake off the immune system so it can attack the cancer. The same released brake can let the immune system inflame healthy tissue. Those reactions are called immune-related adverse events, or irAEs, and they behave more like a temporary autoimmune disease than like a drug allergy.
They can involve almost any organ. Most show up in the first few weeks to months of treatment, but they can appear after a single dose or months after the last one. Because the immune system has a long memory, an irAE sometimes needs weeks of treatment to settle.
The severity of each reaction is scored on a standard 1-to-4 scale called CTCAE (Common Terminology Criteria for Adverse Events): grade 1 is mild, grade 2 moderate, grade 3 severe, grade 4 life-threatening. That grade, along with which organ is affected, is what drives every decision about steroids and about holding or stopping the drug.
The most common irAE. Usually an itchy rash or dry skin; less often patches of lost pigment (vitiligo). Managed with moisturizers, topical steroid creams, and antihistamines. A rare but serious blistering rash or a rash covering much of the body is treated urgently and can mean stopping the drug.
Loose stools, more frequent stools, cramping, or blood or mucus in the stool. Mild cases are managed with anti-diarrheal medicine and fluids; more than a few extra stools a day, or any blood, prompts holding the drug and starting corticosteroids. Steroid-resistant colitis is treated with a second drug such as infliximab.
Usually silent and picked up as rising liver enzymes on routine bloodwork; sometimes yellowing of the skin or eyes, dark urine, or right-sided abdominal pain. Managed by holding the drug and, if significant, corticosteroids.
The thyroid is affected most often — first an overactive phase, then an underactive one needing thyroid hormone tablets. Less commonly the pituitary gland (hypophysitis) or adrenal glands are involved, causing severe fatigue, low blood pressure, or low sodium; rarely, the pancreas, causing sudden diabetes. These are discussed in more detail below.
Inflammation of lung tissue causing a new or worsening cough, breathlessness, or chest tightness. It is uncommon but potentially serious, so any new breathing symptom is checked promptly with a scan. It usually means holding the drug and starting corticosteroids, and moderate-to-severe cases often mean stopping it for good.
Usually detected as a rising creatinine level on blood tests, with few symptoms. Managed by holding the drug and, when needed, corticosteroids; kidney function usually recovers.
Inflammation of the heart muscle (myocarditis), and neurologic reactions affecting nerves or muscles (weakness, drooping eyelids, trouble swallowing or breathing, numbness that spreads), are uncommon but can be dangerous. They are treated as emergencies with high-dose steroids and usually permanent discontinuation of the drug.
Because several irAEs cause no symptoms until they are advanced, monitoring is built into every cycle:
Keeping a simple daily note of new symptoms between visits helps the team catch a reaction while it is still mild and easy to reverse.
National guidelines from the American Society of Clinical Oncology and others tie management to the CTCAE grade:
A course of steroids that lasts more than a few weeks comes with its own supportive care — stomach protection, sometimes an antibiotic to prevent a specific pneumonia, and monitoring of blood sugar and bone health. Taking steroids for an irAE does not appear to cancel out immunotherapy's benefit against the cancer.
Endocrine irAEs are the main exception to the "hold and treat with steroids" pattern. When the immune system damages a hormone gland, the missing hormone often does not come back — but it can be replaced, and treatment can usually continue.
Once the hormone is replaced and the person is stable, the PD-1 inhibitor is generally resumed. An endocrinologist typically co-manages these situations.
In someone with a transplanted kidney, liver, heart, or lung, releasing the immune brake can make the immune system attack the donor organ. In published series, roughly 40% of solid-organ transplant recipients treated with a checkpoint inhibitor experienced rejection, and many lost the organ.
Managing this is different from managing a standard irAE: it involves the transplant team, close monitoring of organ function, adjustments to anti-rejection medication, and sometimes preventive steroids from the start. It is one reason non-immunotherapy treatments are often considered first — see advanced SCC in transplant recipients and immunosuppressed patients.
Do not wait for your next appointment if you have:
Tell any clinician you see — including in an emergency room — that you are on immunotherapy, because the treatment for these reactions (steroids and other immune suppressants) is different from the usual approach.
The side effects of PD-1 immunotherapy come from an over-active immune system rather than a toxic drug, so the response is to calm that inflammation — usually with corticosteroids — and to decide, based on how severe the reaction is and which organ is involved, whether to continue, pause, or stop. Routine bloodwork and a low threshold for reporting symptoms are what keep most reactions mild and reversible.
Some effects, especially on hormone glands, are permanent and need lifelong replacement — but even then, treatment against the cancer can often continue. For how these drugs work and what they achieve, see how immunotherapy treats advanced SCC.
Disclaimer: This article is for educational purposes only and not a substitute for professional medical advice. Always consult a qualified dermatologist or oncologist about your personal diagnosis and treatment plan.
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