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 eligible for curative surgery or curative radiation therapy. As an immune checkpoint inhibitor, while it activates the immune system to fight 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 ≥40mg per day).

Outcome: Pneumonitis resolved in 62% of patients; 1.3% of patients permanently discontinued treatment due to this condition.

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 ≥40mg per day).

Outcome: Colitis resolved in 80% of patients; 0.2% of patients permanently discontinued treatment.

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 ≥40mg per day).

Outcome: Hepatitis resolved in 64% of patients; 0.9% of patients permanently discontinued treatment.

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 Grade 3 case).

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); resolved in 38% of patients.

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 ≥40mg per day).

Outcome: Nephritis resolved in all patients; 0.2% of patients permanently discontinued treatment.

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 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: Permanently discontinue treatment.

Other Grade 3 immune-mediated reactions: Temporarily withhold administration; Grade 4 immune-mediated reactions: Permanently discontinue treatment.

Grade 1-2 infusion reactions: Interrupt or slow down the infusion; Grade 3-4 infusion reactions: Permanently discontinue treatment.

Monitoring Requirements

Baseline Assessment: Conduct a comprehensive evaluation of the patient’s physical condition, including laboratory tests for liver function, thyroid function, etc.

Monitoring During Treatment: Regularly monitor clinical symptoms and signs, especially manifestations of immune-related adverse reactions.

Regularly check clinical biochemical indicators such as liver function and thyroid function.

Promptly evaluate and intervene in patients who develop symptoms of adverse reactions.