From the Guidelines
Pembrolizumab therapy can cause significant immune-related adverse events, including fatigue, rash, pruritus, diarrhea, nausea, and decreased appetite, as well as more serious events like pneumonitis, colitis, hepatitis, nephritis, and endocrinopathies, which require careful monitoring and management, as reported in the most recent study 1.
Common Complications
- Fatigue
- Rash
- Pruritus
- Diarrhea
- Nausea
- Decreased appetite
Serious Immune-Related Adverse Events
- Pneumonitis
- Colitis
- Hepatitis
- Nephritis
- Endocrinopathies (thyroid disorders, hypophysitis, adrenal insufficiency, type 1 diabetes)
- Skin reactions
Management of Complications
- Mild (Grade 1) reactions: pembrolizumab can often be continued with close monitoring
- Moderate (Grade 2) reactions: pembrolizumab should be withheld and corticosteroids (typically prednisone 0.5-1 mg/kg/day or equivalent) initiated
- Severe or life-threatening reactions (Grade 3-4): pembrolizumab should be permanently discontinued and high-dose corticosteroids (prednisone 1-2 mg/kg/day or equivalent) administered, with a slow taper over at least 4-6 weeks once symptoms improve, as recommended in the study 1
Additional Interventions
- Endocrinopathies often require hormone replacement therapy
- Severe colitis may need additional immunosuppression with infliximab (5 mg/kg) if not improving after 3-5 days of steroids
Patient Education and Multidisciplinary Approach
- Patients should be educated about reporting symptoms promptly
- A multidisciplinary approach involving oncologists, organ specialists, and endocrinologists is essential for optimal management of these immune-related adverse events, as noted in the study 1
From the FDA Drug Label
In animal models, inhibition of PD-1/PD-L1 signaling increased the severity of some infections and enhanced inflammatory responses. PD-1 blockade using a primate anti-PD-1 antibody was also shown to exacerbate M. tuberculosis infection in rhesus macaques. Administration of pembrolizumab in chimpanzees with naturally occurring chronic hepatitis B infection resulted in two out of four animals with significantly increased levels of serum ALT, AST, and GGT, which persisted for at least 1 month after discontinuation of pembrolizumab.
The known complications of pembrolizumab therapy include:
- Increased severity of infections: such as Mycobacterium tuberculosis infection
- Enhanced inflammatory responses
- Exacerbation of hepatitis B infection: as seen in chimpanzees with chronic hepatitis B infection
- Elevated liver enzymes: such as ALT, AST, and GGT 2
From the Research
Complications of Pembrolizumab Therapy
- Immune-related adverse events (irAEs) such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes have been associated with pembrolizumab therapy 3
- Multiple autoimmune toxicities, including type 1 diabetes, pneumonitis, hypothyroidism, and polymyalgia rheumatica, can occur in a single patient, especially in elderly individuals 3
- Delayed immune-related hepatitis can occur after 24 months of treatment with pembrolizumab, even after cessation of therapy 4
- Simultaneous and multiple irAEs, including myasthenia gravis, myositis, hepatitis, and pityriasis lichenoides, can occur in patients receiving pembrolizumab therapy 5
Management of Complications
- Immunotherapy should be indefinitely stopped in cases of multiple irAEs 3
- Steroids can be effective in managing irAEs, such as pneumonitis, colitis, and pancreatitis 3, 6
- Thyroid replacement therapy can be used to manage thyroid dysfunction 3
- Insulin therapy can be used to manage type 1 diabetes 3
- Multidisciplinary team management is crucial to prevent further morbidity and mortality 3