Does a patient who received pembrolizumab (pembrolizumab) infusion 5 hours ago with a fever (hyperthermia) of 101.3°F and no other symptoms need to go to the emergency room (ER)?

Management of Isolated Fever After Pembrolizumab Infusion

This patient does not need to go to the ER at this time, as isolated low-grade fever (101.3°F) occurring 5 hours post-pembrolizumab infusion without other symptoms most likely represents a mild infusion-related reaction that can be managed with symptomatic treatment and close outpatient monitoring. 1

Clinical Context and Timing

• Fever occurring on the first day of pembrolizumab strongly suggests an infusion-related reaction rather than a delayed immune-related adverse event (irAE), as inflammatory irAEs typically present within the first 2 cycles but not during or immediately after the actual infusion 1
• Infusion reactions with pembrolizumab occur in approximately 3% of patients and are typically mild, consisting of fever, chills, headache, or nausea 2
• Most infusion reactions associated with immune checkpoint inhibitors are mild, with severe or high-grade reactions occurring in <1% of patients 2

Immediate Management Algorithm

Grade 1-2 Infusion Reaction Management:

• Administer acetaminophen 650-1000 mg orally for fever control 1
• Consider diphenhydramine 25-50 mg orally for additional symptom relief 1
• Monitor vital signs closely for the next 24-48 hours for progression to Grade 3-4 reaction 1
• Instruct patient to monitor temperature every 4-6 hours 1

Red Flags Requiring ER Evaluation

The patient SHOULD go to the ER if any of the following develop:

• Temperature ≥40°C (104°F) 1
• Hypotension (systolic BP <90 mmHg or drop ≥30 mmHg from baseline) 2
• Respiratory symptoms: dyspnea, chest tightness, bronchospasm, or oxygen saturation <92% 2, 3
• Cardiovascular symptoms: chest pain, irregular heartbeat, or dizziness 3
• Severe skin reactions: urticaria, angioedema, or rash with blistering 2, 3
• Gastrointestinal symptoms: severe diarrhea, abdominal pain, or bloody stools 3
• Neurological symptoms: confusion, severe headache, or altered mental status 3
• Signs of organ-specific toxicity: jaundice, dark urine, decreased urine output 3

Critical Distinction: Infusion Reaction vs. Immune-Related Adverse Events

• Infusion reactions occur during or within 24 hours of infusion and include fever, chills, flushing, and mild constitutional symptoms 2
• Immune-related adverse events typically present later (within first 2 cycles but not immediately post-infusion) and involve organ-specific symptoms such as pneumonitis (cough, dyspnea), colitis (diarrhea), or hepatitis (jaundice) 2, 4
• The 5-hour timeframe with isolated fever and no organ-specific symptoms makes this consistent with a mild infusion reaction 1

Monitoring Plan for Next 24-48 Hours

Outpatient monitoring should include:

• Temperature checks every 4-6 hours 1
• Assessment for development of respiratory symptoms (cough, dyspnea, chest pain) that could indicate early pneumonitis 1, 5
• Monitoring for gastrointestinal symptoms (diarrhea, abdominal pain) suggesting colitis 1
• Observation for skin changes beyond simple flushing 4
• Contact oncology team if fever persists >24 hours or any new symptoms develop 1

Prevention for Future Infusions

For subsequent pembrolizumab doses:

• Premedicate with acetaminophen 650-1000 mg and diphenhydramine 25-50 mg 30-60 minutes before infusion 2, 1
• Consider slower infusion rate for next dose 2, 1
• Do not restart at full infusion rate if interruption was required 1

Important Caveats

• While isolated fever is likely benign, pembrolizumab can cause serious immune-mediated adverse events including pneumonitis, which can present with fever and progress rapidly 5
• Superimposed bacterial infection must be considered if fever persists beyond 24-48 hours or if patient develops neutropenia, as the prognosis of pembrolizumab-induced pneumonitis with superimposed bacterial pneumonia is poor 5
• Fever accompanied by any organ-specific symptoms requires immediate evaluation for immune-mediated organ toxicity 1
• The patient should have direct access to contact their oncology team for any concerning developments 1

In summary, this presentation is consistent with a mild infusion reaction that can be safely managed at home with symptomatic treatment and close monitoring, reserving ER evaluation for development of severe symptoms or organ-specific toxicity.