Keytruda (Pembrolizumab) Side Effects in Patients with Autoimmune Disease or Organ Transplantation History
Critical Contraindication Warning
Keytruda is contraindicated or extremely high-risk in patients with a history of solid organ transplantation, as rejection occurred in 37.5% of liver transplant recipients treated with immune checkpoint inhibitors, with 75% progressing to end-stage organ failure. 1
Special Population Considerations
Patients with History of Autoimmune Disease
Patients with active autoimmune disease requiring systemic immunosuppression were excluded from clinical trials and should generally not receive Keytruda. 1
- Immune checkpoint blockers may interfere with immunosuppressive therapy and/or result in exacerbation of the underlying autoimmune disease 1
- Limited experience exists only from case reports in patients with ulcerative colitis, multiple sclerosis, or rheumatoid arthritis 1
- If treatment is considered, it should only be for patients with organ-specific autoimmunity (e.g., vitiligo, adequately controlled endocrine deficiencies with substitutive treatment), and requires close monitoring in partnership with the physician managing the autoimmune disease 1
Patients with History of Organ Transplantation
Immune checkpoint inhibitors including Keytruda should be avoided in solid organ transplant recipients due to the high risk of graft rejection and organ failure. 1
- Rejection risk is 37.5% in transplant recipients, with 75% of rejections progressing to end-stage organ failure 1
- Patients with history of stem cell or solid organ transplantation were specifically excluded from the IMbrave150 trial and other major clinical trials 1
Common Side Effects by System
Immune-Related Adverse Events (irAEs)
Early identification and treatment of immune-mediated adverse events are essential to limit their duration and severity, as these can occur at any time during treatment or even after discontinuation. 1
Gastrointestinal
- Diarrhea (36-62% all grades, 2.6-10% grade 3-4) 2
- Colitis (2.3% leading to treatment interruption) 2
- Nausea (19-41% all grades) 2
- Vomiting (19-26% all grades) 2
- Abdominal pain (11-27% all grades) 2
- Stomatitis/glossitis (rare but reported, may require corticosteroid treatment) 3
Endocrine
- Hypothyroidism (11-57% all grades) 2
- Hyperthyroidism (12% all grades) 2
- Adrenal insufficiency (1% leading to discontinuation) 2
Hepatobiliary
- Hepatotoxicity (14-25% all grades, 3.7-9% grade 3-4) 2
- Increased ALT (20-52% all grades, 1.6-7% grade 3-4) 2
- Increased AST (34-58% all grades, 3-7% grade 3-4) 2
Renal
- Acute kidney injury (13-21% all grades, 1.2-5% grade 3-4) 2
- Increased creatinine (32-61% all grades, 2.6-5% grade 3-4) 2
- Proteinuria (30% all grades, 8% grade 3-4) 2
Dermatologic
Pulmonary
Cardiovascular
- Atrial fibrillation (higher risk in older males with pre-existing cardiovascular risk factors or diseases, previous autoimmune diseases, and solid organ transplant recipients) 1
- Hypertension (23-56% all grades, 9-29% grade 3-4) 2
Pancreatic
- Pancreatitis (reported case of pembrolizumab-induced acute pancreatitis) 4
Hematologic Abnormalities
- Anemia (28-80% all grades, 0.5-35% grade 3-4) 2
- Lymphopenia (54-64% all grades, 9-35% grade 3-4) 2
- Thrombocytopenia (14-57% all grades, 1.3-19% grade 3-4) 2
- Neutropenia (31-73% all grades, 4-43% grade 3-4) 2
Metabolic Abnormalities
- Hyperglycemia (38-55% all grades, 1.3-8% grade 3-4) 2
- Hyponatremia (21-41% all grades, 3.3-14% grade 3-4) 2
- Hypoalbuminemia (34-46% all grades, 0.3-5% grade 3-4) 2
Constitutional Symptoms
- Fatigue/asthenia (40-63% all grades, 1.2-9% grade 3-4) 2
- Pyrexia (19% all grades, 3.3% leading to treatment interruption) 2
- Decreased appetite (21-41% all grades) 2
Management Algorithm
Baseline Assessment (Before Starting Keytruda)
Physical examination, laboratory tests, and imaging performed at baseline serve as reference for any clinical, biological, or imaging abnormality occurring under treatment. 1
Monitoring During Treatment
Patients should be under close monitoring as immune-related adverse events may occur at any time: at the beginning, during, or even after treatment discontinuation, with surveillance continuing for 1 year after immunotherapy discontinuation. 1
Treatment Interruption and Corticosteroid Management
Based on adverse event severity, immunotherapy treatment may be suspended and/or corticosteroids administered, with life-threatening or recurrent serious adverse events leading to immunotherapy termination. 1
- For severe adverse events requiring prolonged corticosteroid immunosuppression, patients are eligible for antibiotic prophylaxis to prevent opportunistic infections 1
- When corticosteroids are stopped, a gradual decrease over at least 1 month from improvement must be initiated, as too rapid tapering may cause relapse or worsening of adverse effects 1
- The corticosteroid tapering scheme should be planned with the organ specialist referral 1
Treatment Discontinuation Rates
- Overall discontinuation due to adverse reactions: 8-21% of patients 2
- Most common reasons for discontinuation: increased ALT (1.6%), colitis (1-2.3%), adrenal insufficiency (1%), ascites (2%) 2
Critical Pitfalls to Avoid
Do not use Keytruda in solid organ transplant recipients - rejection risk is unacceptably high (37.5%) with 75% progressing to organ failure 1
Do not use in patients with active autoimmune disease requiring systemic immunosuppression - these patients were excluded from trials and may experience disease exacerbation 1
Do not taper corticosteroids too rapidly - must taper over at least 1 month to prevent relapse of immune-related adverse events 1
Do not stop monitoring after treatment discontinuation - immune-related adverse events can occur even after stopping therapy, requiring surveillance for 1 year 1