From the Guidelines
Keytruda (pembrolizumab) can cause immune-mediated hepatitis, a potentially serious liver injury that requires prompt recognition and management, and the most recent evidence suggests that for severe hepatitis, Keytruda should be permanently discontinued and prednisone administered at a dose of 1-2 mg/kg/day 1.
Management of Keytruda Induced Liver Injury
If liver injury is suspected, immediately check liver function tests and consider temporarily withholding Keytruda depending on severity.
- For mild hepatitis (AST/ALT 1-3 times upper limit of normal), close monitoring may be sufficient, as suggested by the guidelines for managing immunotherapy-related toxicity 1.
- For moderate hepatitis (AST/ALT 3-5 times upper limit), withhold Keytruda and start prednisone 0.5-1 mg/kg/day, as recommended by recent studies on the management of immune-mediated liver injury 1.
- For severe hepatitis (AST/ALT >5 times upper limit), permanently discontinue Keytruda and administer prednisone 1-2 mg/kg/day, and taper steroids gradually over 4-6 weeks once liver enzymes improve, as advised by the latest guidelines on immunotherapy-related toxicity 1.
Patient Education and Monitoring
Patients should be educated about symptoms including fatigue, jaundice, right upper quadrant pain, and dark urine.
- This liver injury occurs because Keytruda, by blocking PD-1 receptors to enhance anti-tumor immunity, can also trigger immune cells to attack healthy liver tissue.
- Regular liver function monitoring is essential throughout treatment, typically before each dose, to detect hepatotoxicity early before it becomes severe, as emphasized by recent studies on the safety of ICIs in patients with pre-existing chronic liver disease 1.
From the FDA Drug Label
Hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%) The most common adverse reaction (>1%) resulting in permanent discontinuation of KEYTRUDA, axitinib, or the combination was hepatotoxicity (13%) The most common adverse reactions (>10%) resulting in interruption of KEYTRUDA were hepatotoxicity (14%) Hepatotoxicity§3920254.9
Keytruda induced liver injury is a known adverse reaction. The incidence of hepatotoxicity was 25.9% (all grades) and 21.5% (grades 3-4) in patients receiving KEYTRUDA with lenvatinib, and 39.2% (all grades) and 4.9% (grades 3-4) in patients receiving KEYTRUDA with axitinib. Hepatotoxicity was also a common cause of permanent discontinuation and interruption of KEYTRUDA. 2 2
From the Research
Keytruda Induced Liver Injury
- Keytruda (pembrolizumab) is an inhibitor of programmed cell death receptor-1 (PD-1) that has been associated with liver injury in some patients 3, 4, 5.
- A case report described a patient with pulmonary metastatic liver cancer who developed severe liver dysfunction after receiving pembrolizumab treatment, which was diagnosed as pembrolizumab-induced immune-related hepatitis 3.
- Another study found that liver injury occurred in 14.3% of patients receiving pembrolizumab, but only 28.6% of these cases were adjudicated as probable drug-induced hepatotoxicity 4.
- The study also found that patients with liver injury had poorer outcomes, including lower tumor remission rates and higher mortality, compared to those without liver injury 4.
- A case report presented a patient who developed grade 4 pembrolizumab-induced liver toxicity, which was associated with an excellent treatment response 5.
- It is worth noting that one of the studies provided is not relevant to the topic of Keytruda induced liver injury, as it discusses thyroid function in changing weather conditions 6.