A Wolf in Sheep's Clothing: Systemic Immune Activation Post Immunotherapy

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Immune checkpoint inhibitors (ICIs) are standard cancer treatments.
• Immune-related adverse events (irAEs) are common with ICIs.
• Fever is a frequent irAE, but can indicate rare Systemic Immune Activation (SIA) or acquired Hemophagocytic Lymphohistiocytosis (HLH).

Purpose of the Study:

• To report on the incidence and characteristics of SIA/HLH in patients treated with ICIs.
• To describe clinical presentation, treatment, and outcomes of SIA/HLH post-ICI.

Main Methods:

• Retrospective review of patients receiving ICIs at a single institution (May 2014 - Nov 2019).
• Inclusion criteria: fever ≥ 38°C or chills/rigors within 6 weeks of ICI initiation.
• Clinical data collection for identified patients.

Main Results:

• Three patients met diagnostic criteria for SIA/HLH.
• Median time to symptom onset was 10 days.
• High-dose steroids were first-line treatment; other agents considered for refractory cases.

Conclusions:

• SIA/HLH is a rare, potentially fatal irAE following ICI therapy.
• Presents with fever and non-specific symptoms.
• Early diagnosis and prompt management are critical for improved outcomes.