What are the side effects of Keytruda (pembrolizumab)?

Keytruda (Pembrolizumab) Side Effects

Pembrolizumab (Keytruda) can cause serious immune-mediated adverse events that require careful monitoring, with the most common side effects being fatigue, skin reactions, gastrointestinal issues, and endocrinopathies.

Common Side Effects

Pembrolizumab is associated with a range of side effects that vary in severity. According to the FDA label and clinical guidelines, the most common side effects include:

• Fatigue (very common, affecting >20% of patients) 1, 2
• Skin reactions:
  • Rash (common) 1, 2
  • Pruritus (itching) 1, 2
  • Vitiligo 1
• Gastrointestinal issues:
  • Diarrhea 1, 2
  • Nausea 1, 2
  • Constipation 2
  • Decreased appetite 1, 2
• Respiratory symptoms:
  • Cough 2
  • Dyspnea (shortness of breath) 2
• Musculoskeletal pain 2

Serious Immune-Mediated Adverse Events

Pembrolizumab works by enhancing the immune system's ability to detect and fight cancer cells, but this can lead to immune-related adverse events (irAEs) where the immune system attacks healthy tissues:

1. Endocrinopathies

• Thyroid disorders (hypothyroidism, hyperthyroidism) 1
• Hypophysitis (inflammation of the pituitary gland) 1, 3
• Adrenal insufficiency 1, 3
• Type 1 diabetes (rare but can lead to diabetic ketoacidosis) 1

2. Gastrointestinal Toxicities

• Colitis (inflammation of the colon) 1
• Hepatitis (elevated liver enzymes ALT/AST) 1
• Pancreatitis (elevated lipase and amylase) 1

3. Pulmonary Toxicities

• Pneumonitis (inflammation of lung tissue) - occurs in approximately 3-7% of patients and is one of the most serious side effects 1

4. Other Serious irAEs

• Nephritis (kidney inflammation) 1
• Myocarditis (heart muscle inflammation) - rare but potentially life-threatening 1
• Neurological toxicities (neuropathy, encephalopathy, Guillain-Barré syndrome) 1
• Severe skin reactions (Stevens-Johnson syndrome, DRESS) 1

Monitoring and Management

The management of pembrolizumab side effects requires:

1. Early identification - patients should report new or worsening symptoms promptly 1
2. Baseline assessments before starting therapy to serve as reference points 1
3. Regular monitoring of clinical symptoms and laboratory values during treatment
4. Prompt intervention - often involving corticosteroids for immune-related adverse events 1

Special Considerations

• Timing of side effects: Immune-related adverse events can occur at any time - during treatment or even after discontinuation 1
• Patient education: Patients should be informed about potential side effects and the importance of reporting symptoms early 1
• Healthcare coordination: Communication between oncologists and other healthcare providers is essential 1

Risk Factors

While pembrolizumab can be used across various cancer types, certain factors may influence the risk of side effects:

• Previous autoimmune conditions (though not an absolute contraindication)
• Prior organ transplantation
• Previous or concurrent radiation therapy

Documentation Tools

Many centers use tools like an "Immunotherapy Patient Card" to help patients recognize and report potential immune-related side effects promptly 1.

Remember that while these side effects can be serious, most are manageable if detected early and treated appropriately. The benefit-risk profile of pembrolizumab remains favorable for approved indications when patients are properly monitored.