Distinct autoantibody profiles across checkpoint inhibitor types and toxicities

Area of Science:

• Oncology
• Immunology
• Clinical Trials

Background:

• Immune checkpoint inhibitors (ICI) are crucial in cancer therapy, often used in combination.
• Understanding the specific effects of different ICI categories on the immune system is vital for optimizing treatment and managing side effects.
• Hodgkin Lymphoma treatment has evolved with combination immunotherapies.

Purpose of the Study:

• To investigate the dynamic changes in circulating autoantibodies in Hodgkin Lymphoma patients treated with combination ICI therapies.
• To compare the effects of brentuximab vedotin (BV) plus ipilimumab, BV plus nivolumab, and BV plus ipilimumab-nivolumab on autoantibody profiles.
• To correlate autoantibody changes with immune-related adverse events (irAEs).

Main Methods:

• Analysis of autoantibody levels from blood samples collected at baseline and Cycle 2 Day 1 (C2D1) in the E4412 trial (NCT01896999).
• Testing of 112 distinct autoantibodies to characterize immune responses.
• Comparison of autoantibody profiles across different ICI combination arms (BV+ipilimumab, BV+nivolumab, BV+ipilimumab-nivolumab).

Main Results:

• Ipililumab-containing regimens generally led to increased autoantibody levels, whereas the nivolumab arm showed decreases.
• Out of 15 autoantibodies with significant C2D1 changes, all nivolumab cases decreased, while over 90% of ipililumab cases increased.
• Distinct autoantibody profiles were observed correlating with specific irAEs, such as increased autoantibodies with rash and decreased autoantibodies with liver toxicity.

Conclusions:

• Dynamic autoantibody profiles vary significantly based on the category of immune checkpoint inhibitor used.
• The type of immune-related adverse event is associated with specific patterns of autoantibody changes.
• These findings may inform clinical monitoring strategies and the management of irAEs in patients receiving combination ICI therapy.