Management of Fever >101°F on First Day of Pembrolizumab

Immediate Assessment and Grading

• The American Society of Clinical Oncology recommends that a patient developing fever over 101°F on the first day of pembrolizumab should be assessed for a Grade 1-2 infusion reaction, which occurs in approximately 3% of patients, and managed with symptomatic treatment and close monitoring 1
• The National Comprehensive Cancer Network guidelines suggest that fever on day one strongly suggests an infusion-related reaction rather than a delayed immune-related adverse event, as inflammatory irAEs typically present within the first 2 cycles but not during the actual infusion 2

Acute Management Algorithm

• The European Society for Medical Oncology recommends stopping or slowing the infusion rate immediately and administering acetaminophen and diphenhydramine as symptomatic treatment for Grade 1-2 infusion reactions 1
• The American College of Physicians recommends monitoring vital signs closely for progression to Grade 3-4 reaction and restarting infusion at a slower rate once fever and symptoms resolve, with continued close monitoring 1

Post-Infusion Monitoring

• The National Comprehensive Cancer Network guidelines recommend monitoring for 24-48 hours for development of other immune-related symptoms that may indicate early pneumonitis, colitis, hepatitis, or other organ-specific irAEs 2

Premedication for Subsequent Doses

• The European Society for Medical Oncology guidelines suggest considering premedication with antipyretics and antihistamines for all subsequent pembrolizumab infusions if infusion reaction occurred 1

Critical Pitfalls to Avoid

• The American Society of Clinical Oncology recommends not restarting at full infusion rate after interruption for infusion reaction, and instead restarting at a slower rate 1

When to Escalate Care

• The National Comprehensive Cancer Network guidelines recommend that any fever accompanied by organ-specific symptoms requires immediate evaluation for immune-mediated organ toxicity 2
• The American College of Physicians recommends considering hospitalization for Grade 3-4 fever (>40°C or with complications) with high-dose corticosteroids 3