What are the adverse drug reactions (ADRs) of serplulimab?

Serplulimab Adverse Drug Reactions

Serplulimab, as a PD-1 inhibitor, causes immune-related adverse events (irAEs) affecting multiple organ systems, with grade 3 or higher treatment-related adverse events occurring in approximately 47-53% of patients when combined with chemotherapy.

Overall Safety Profile

Based on the FDA drug label 1, serplulimab can cause:

• Febrile response
• Infection at injection site
• Venous thrombosis or phlebitis
• Extravasation
• Hypervolemia

However, as a PD-1 inhibitor, the more clinically relevant adverse reactions follow the class-specific immune-related pattern 2.

Common Adverse Events by Organ System

Endocrine Toxicities

• Thyroid dysfunction is particularly notable with serplulimab 3

  • Can manifest as hyperthyroidism initially, followed by hypothyroidism in the same patient
  • Severe hyperthyroidism may occur as early as the second treatment cycle
  • Usually reversible after treatment cessation
  • Critical pitfall: Monitor thyroid function at baseline and each cycle, as the biphasic pattern (hyper→hypo) is unpredictable

• Immune checkpoint inhibitor-induced diabetes mellitus (ICI-DM) 4

  • Can present with diabetic ketoacidosis (DKA)
  • May occur early in treatment or delayed (up to 2 years)
  • Characterized by C-peptide deficiency
  • Often negative for diabetes-related autoantibodies
  • Requires permanent insulin therapy - this is not reversible
  • Monitor blood glucose and HbA1c before and during treatment

Pulmonary Toxicities

• Checkpoint inhibitor pneumonitis (CIP) 5
  • Can be severe (grade 4) and life-threatening
  • Higher risk in patients with preexisting COPD (especially GOLD stage IV)
  • Presents with acute dyspnea, chest tightness, and hypoxemia
  • New bilateral pulmonary infiltrates on CT
  • Management: High-dose methylprednisolone, IVIG, and permanent discontinuation of serplulimab
  • Requires extensive workup to exclude infection, COPD exacerbation, and tumor progression

Most Frequently Affected Organs (Based on PD-1 Class Effects) 2

• Skin: Often the first to develop
• Gastrointestinal: Colitis
• Hepatic: Elevated liver enzymes
• Pulmonary: Pneumonitis (as detailed above)
• Endocrine: Thyroid, pituitary, pancreas

Incidence Rates

From clinical trial data:

ASTRUM-007 (First-line ESCC) 6:

• Grade ≥3 treatment-related adverse events: 53% (serplulimab + chemotherapy)
• Comparable to placebo + chemotherapy: 48%

ASTRUM-006 (Perioperative gastric cancer) 7:

• Grade ≥3 treatment-related adverse events: 47% (serplulimab group)
• Lower than chemotherapy alone: 59%
• Treatment discontinuation due to adverse events: 7%

Real-world data (ES-SCLC retreatment) 8:

• Grade ≥3 adverse events: 29.9% (serplulimab monotherapy)
• Similar to chemotherapy: 34.4%

Key Clinical Considerations

Timing of Onset

• Endocrine toxicities: Can occur anytime from cycle 2 to 2+ years
• Pneumonitis: Can occur within days of administration
• Most irAEs: Typically within first 8-12 weeks (based on PD-1 class data) 2

Severity Comparison

Serplulimab demonstrates a more favorable safety profile compared to:

• CTLA-4 inhibitors (ipilimumab: 10-27% grade 3-4 irAEs) 2
• Comparable to other PD-1 inhibitors (nivolumab: 12-20% grade 3-4; pembrolizumab: similar range) 2

Critical Management Pitfalls to Avoid

1. Do not assume thyroid dysfunction is unidirectional - patients can transition from hyperthyroidism to hypothyroidism 3

2. Do not restart serplulimab after grade 4 pneumonitis - permanent discontinuation is required 5

3. Do not delay insulin in ICI-DM - this is typically permanent beta-cell destruction requiring immediate insulin therapy 4

4. Do not attribute new respiratory symptoms solely to underlying COPD - maintain high suspicion for CIP even in patients with preexisting lung disease 5

5. Monitor glucose even without diabetes risk factors - ICI-DM can occur in patients without typical risk factors 4

Monitoring Algorithm

Baseline:

• Thyroid function (TSH, free T4)
• Blood glucose and HbA1c
• Liver enzymes
• Baseline chest imaging

Each cycle:

• Thyroid function
• Blood glucose
• Clinical assessment for respiratory symptoms

As clinically indicated:

• Chest CT for new respiratory symptoms
• Comprehensive metabolic panel for suspected hepatitis or colitis