Cemiplimab is a programmed death receptor-1 (PD-1) blocking antibody indicated for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation therapy. As an immune checkpoint inhibitor, while it activates the immune system to combat tumors, it may also trigger a series of immune-related adverse reactions.
What Are the Side Effects of Cemiplimab?
Common Side Effects
Fatigue: Occurs in approximately 29% of patients, with 2% experiencing severe (grade 3-4) fatigue.
Rash: Occurs in approximately 25% of patients, with 1.2% experiencing severe (grade 3-4) rash.
Diarrhea: Occurs in approximately 22% of patients, with 0.6% experiencing severe (grade 3-4) diarrhea.
Severe Side Effects of Cemiplimab Requiring Vigilance
Immune-Mediated Pneumonitis
Incidence: 2.4% (among 534 patients).
Severity: Includes 0.2% fatal cases, 0.7% grade 3 cases, and 1.3% grade 2 cases.
Management: Requires systemic corticosteroid treatment (85% of patients need a prednisone-equivalent dose of ≥40 mg/day).
Outcome: Pneumonitis resolved in 62% of patients; 1.3% of patients discontinued treatment permanently due to this adverse reaction.
Immune-Mediated Colitis
Incidence: 0.9%.
Severity: 0.4% grade 3 cases and 0.6% grade 2 cases.
Management: All patients require corticosteroid treatment (60% need a prednisone-equivalent dose of ≥40 mg/day).
Outcome: Colitis resolved in 80% of patients; 0.2% of patients discontinued treatment permanently.
Immune-Mediated Hepatitis
Incidence: 2.1%.
Severity: Includes 0.2% fatal cases, 0.2% grade 4 cases, and 1.7% grade 3 cases.
Management: All patients require corticosteroid treatment (91% need a prednisone-equivalent dose of ≥40 mg/day).
Outcome: Hepatitis resolved in 64% of patients; 0.9% of patients discontinued treatment permanently.
Immune-Mediated Endocrine Disorders
Adrenal Insufficiency: Incidence of 0.4% (0.2% grade 3 cases and 0.2% grade 2 cases).
Hypophysitis: Incidence of 0.2% (1 case of grade 3).
Hypothyroidism: Incidence of 6% (0.2% grade 3 cases and 5.6% grade 2 cases).
Hyperthyroidism: Incidence of 1.5% (0.2% grade 3 cases and 0.4% grade 2 cases); 38% of cases resolved.
Type 1 Diabetes Mellitus: Incidence of 0.7% (0.4% grade 4 cases and 0.4% grade 3 cases), which may present as diabetic ketoacidosis.
Immune-Mediated Nephritis
Incidence: 0.6% (0.4% grade 3 cases and 0.2% grade 2 cases).
Management: All patients require corticosteroid treatment (67% need a prednisone-equivalent dose of ≥40 mg/day).
Outcome: Nephritis resolved in all patients; 0.2% of patients discontinued treatment permanently.
Precautions for Cemiplimab Administration
Key Principles for Dose Adjustment
Grade 2 pneumonitis, grade 2-3 colitis, transaminase elevation 3-10 times the upper limit of normal (ULN), or total bilirubin elevation up to 3 times ULN: Temporarily withhold administration.
Grade 3-4 pneumonitis, grade 4 colitis, transaminase elevation >10 times ULN, or total bilirubin >3 times ULN: Discontinue administration permanently.
Other grade 3 immune-mediated reactions: Temporarily withhold administration; grade 4 immune-mediated reactions: Discontinue administration permanently.
Grade 1-2 infusion reactions: Interrupt or slow down the infusion rate; grade 3-4 infusion reactions: Discontinue administration permanently.
Monitoring Requirements
Baseline Assessment: Conduct a comprehensive evaluation of the patient’s physical condition, including laboratory tests for liver function and thyroid function.
Monitoring During Treatment: Regularly monitor clinical symptoms and signs, particularly manifestations of immune-mediated adverse reactions.
Periodic Testing: Conduct regular tests of clinical biochemical indicators such as liver function and thyroid function.
Timely Intervention: Promptly evaluate and intervene in patients who develop symptoms of adverse reactions.
