Keytruda (pembrolizumab) is an immunotherapy medication used to treat various cancers. It works by harnessing the body’s immune system to fight cancer cells. However, a potential side effect of this treatment is pneumonitis, which involves inflammation of the lungs. This immune-related adverse event can occur during or after treatment.
Understanding Keytruda and Its Lung Impact
Keytruda, or pembrolizumab, functions as an immune checkpoint inhibitor, specifically targeting the PD-1 (programmed cell death protein 1) pathway. By blocking the interaction between PD-1 on T-cells and its ligand PD-L1 on cancer cells, Keytruda effectively “unleashes” the immune system, allowing it to recognize and attack tumor cells more vigorously. This mechanism can lead to significant anti-tumor responses.
While Keytruda’s action is designed to eliminate cancer, this heightened immune activity can sometimes extend beyond cancer cells and mistakenly target healthy tissues, including the lungs. This “off-target” immune response results in inflammation within the lung tissue, a condition known as pneumonitis.
The occurrence of pneumonitis with immune checkpoint inhibitors like Keytruda is uncommon. Clinical trials have reported an incidence from 1% to 7% for monotherapy, with slightly higher rates in combination therapies. Patients with pre-existing interstitial lung disease or a history of asthma/chronic obstructive pulmonary disease have a higher risk.
Recognizing the Signs
Patients undergoing Keytruda treatment should be aware of symptoms of pneumonitis. Shortness of breath, especially during physical exertion, is a common sign. A persistent, dry cough is another symptom.
Some individuals may experience chest pain, particularly when breathing deeply. Fatigue or low oxygen levels can also accompany these respiratory symptoms. These initial signs can be subtle and might be mistaken for other conditions, such as a respiratory infection or even the progression of cancer.
It is important for patients to report any new or worsening respiratory symptoms to their healthcare team without delay. Early reporting allows for prompt assessment. The median time for symptoms to appear is 2.5 months after starting therapy, but onset can vary, from days to over a year after treatment starts or stops.
Diagnosing and Grading Severity
The diagnostic process for Keytruda pneumonitis involves an evaluation by the healthcare team. It begins with reviewing reported symptoms and a physical examination, including listening to the lungs.
Imaging studies are important for diagnosis, with chest X-rays often used as a first step. However, a chest computed tomography (CT) scan is crucial for visualizing lung inflammation. CT scans can reveal various patterns of pneumonitis, such as organizing pneumonia or non-specific interstitial pneumonia.
Diagnosis involves ruling out other causes of lung symptoms, such as infections (bacterial or viral pneumonia) or cancer progression. This may involve blood tests, sputum cultures, or bronchoscopy for sample collection. Differentiating Keytruda pneumonitis from other conditions ensures the correct treatment approach.
Once pneumonitis is diagnosed, its severity is graded to guide treatment decisions. The Common Terminology Criteria for Adverse Events (CTCAE) is used, classifying pneumonitis from Grade 1 to Grade 5. Grade 1 involves radiographic changes without symptoms, while higher grades signify more severe symptoms, impact on daily activities, and greater lung involvement.
Treatment Approaches
The initial step in managing Keytruda pneumonitis involves discontinuing or temporarily holding the Keytruda treatment, with the decision based on the severity of the lung inflammation. This interruption allows the immune system to calm down and prevents further aggravation of the condition.
Corticosteroids, such as prednisone, are the primary treatment for immune-mediated pneumonitis. These medications work by suppressing the overactive immune response in the lungs and reducing inflammation. Doses typically range from 1 to 2 mg/kg/day of prednisone or its equivalent, and are administered until symptoms improve to a mild level (Grade 1).
Once symptoms have subsided, the corticosteroid dosage is slowly tapered down over at least a month to prevent a rebound of inflammation and allow the body to gradually adjust. Supportive care, such as oxygen therapy, may also be provided if a patient experiences shortness of breath or low oxygen levels. Close monitoring of symptoms and lung function is maintained throughout this period.
For severe or refractory cases that do not respond sufficiently to corticosteroids, other immunosuppressive drugs may be considered. These can include medications like infliximab, cyclophosphamide, or mycophenolate mofetil. These agents are used to further modulate the immune system and reduce lung inflammation, particularly when corticosteroids alone are not enough to control the condition.