Immunotherapy Pneumonitis: Symptoms & Prompt Care

Immune checkpoint inhibitors help your immune system attack cancer by removing some of the controls that normally hold it back. Sometimes the immune system also turns on healthy organs. The National Cancer Institute (NCI) calls this organ-related inflammation and names each type after the organ, using the ending "-itis." Inflammation in the lungs is called pneumonitis.

NCI describes it in one sentence: "Inflammation in the lungs, called pneumonitis, can cause you to feel short of breath and have a bad cough."

That is a short list, and the words matter. Two things count here:

A new cough, or a cough that is getting worse. The patient information from the U.S. National Library of Medicine for pembrolizumab lists "New or worsening cough, shortness of breath, chest pain" among the symptoms that need urgent attention. A cough you have had for years is not the signal. A cough that started after you began immunotherapy, or one that has changed, is.

Breathlessness at less effort than before. This is the measure to use, because "short of breath" is easy to talk yourself out of. Compare against your own recent baseline: if last month you climbed a flight of stairs without stopping and this week you stop halfway, that is the change worth reporting — even if you can still get up the stairs. If you now get breathless walking across a room, or while sitting still, that is further along the same line.

Chest pain or chest discomfort appears alongside cough and breathlessness in the same list of symptoms to act on.

Pneumonitis does not always announce itself. In FDA labeling for pembrolizumab, immune-mediated pneumonitis occurred in 3.4% of patients treated, including fatal cases in 0.1%. Some cases are picked up on imaging done for other reasons, before the person has described many symptoms.

There are two consequences for you. First, if a scan report mentions changes in your lungs, ask your oncology team directly whether pneumonitis is being considered, even if you feel well. Second, do not use "I feel mostly fine" as a reason to hold back a mild new cough. Early pneumonitis and mild pneumonitis can look the same from the inside.

The instruction in the National Library of Medicine's pembrolizumab information is not gentle, and it should not be softened here: "Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment." New or worsening cough, shortness of breath, and chest pain are on that list.

The same phrasing appears in the ipilimumab patient information, where "cough, chest pain, or shortness of breath" is followed by the instruction to "call your doctor immediately or get emergency medical treatment."

NCI adds that your oncologist "may advise you to call him or her first about inflammatory symptoms, or you may be advised to seek emergency medical care." Find out at your next visit which of these your team wants, and where to call outside clinic hours, so you are not deciding it while breathless.

If you go to an emergency department or urgent care, say the name of your immunotherapy drug and when you last received it. Clinicians who do not know you are on a checkpoint inhibitor may reach for pneumonia or a chest infection first. Pneumonitis is not an infection and is not treated with antibiotics.

Since the underlying problem is an immune response that has gone too far, the treatment targets the immune system. NCI states: "Sometimes these side effects are managed with medicines, such as steroids, that work to slow down an overactive immune response."

In pembrolizumab labeling, systemic corticosteroids were required in 67% of patients who developed pneumonitis. The labeled approach is prednisone at 1 to 2 mg/kg/day, or an equivalent, until the reaction improves to Grade 1 or less, then tapered over at least one month. Pneumonitis led to the drug being permanently discontinued in 1.3% of patients and temporarily withheld in 0.9%.

Lung symptoms can begin after treatment has ended. FDA labeling states that "immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody," and that although they usually appear during treatment, they "can also manifest after discontinuation." A new cough or new breathlessness months after your final infusion still belongs to your oncology team.

• National Cancer Institute — Immunotherapy and Organ-Related Inflammation: https://www.cancer.gov/about-cancer/treatment/side-effects/organ-inflammation
• MedlinePlus (National Library of Medicine) — Pembrolizumab Injection: https://medlineplus.gov/druginfo/meds/a614048.html
• MedlinePlus (National Library of Medicine) — Ipilimumab Injection: https://medlineplus.gov/druginfo/meds/a611023.html
• U.S. Food and Drug Administration — KEYTRUDA (pembrolizumab) prescribing information: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125514s158lbl.pdf

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