Distinct autoantibody profiles across checkpoint inhibitor types and toxicities

• Published in: Oncoimmunology Vol. 13; no. 1; p. 2351255
• Main Authors: Mu-Mosley, Hong, von Itzstein, Mitchell S., Fattah, Farjana, Liu, Jialiang, Zhu, Chengsong, Xie, Yang, Wakeland, Edward K., Park, Jason Y., Kahl, Brad S., Diefenbach, Catherine S., Gerber, David E.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 31.12.2024; Taylor & Francis Group
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; biomarkers; Brentuximab Vedotin - therapeutic use; CTLA-4; Female; Hodgkin Disease - drug therapy; Hodgkin Disease - immunology; Humans; immune checkpoint inhibitor; Immune Checkpoint Inhibitors - administration & dosage; Immune Checkpoint Inhibitors - adverse effects; immune-related adverse events; immunotherapy; Ipilimumab - administration & dosage; Ipilimumab - adverse effects; Male; Middle Aged; Nivolumab - administration & dosage; Nivolumab - adverse effects; PD-1; immune checkpoint inhibitor; Autoantibodies; biomarkers; immune-related adverse events; immunotherapy; CTLA-4; PD-1
• ISSN: 2162-402X; 2162-402X
• DOI: 10.1080/2162402X.2024.2351255

Immune checkpoint inhibitors (ICI) are increasingly used in combination. To understand the effects of different ICI categories, we characterized changes in circulating autoantibodies in patients enrolled in the E4412 trial (NCT01896999) of brentuximab vedotin (BV) plus ipilimumab, BV plus nivolumab, or BV plus ipilimumab-nivolumab for Hodgkin Lymphoma. Cycle 2 Day 1 (C2D1) autoantibody levels were compared to pre-treatment baseline. Across 112 autoantibodies tested, we generally observed increases in ipilimumab-containing regimens, with decreases noted in the nivolumab arm. Among 15 autoantibodies with significant changes at C2D1, all nivolumab cases exhibited decreases, with more than 90% of ipilimumab-exposed cases showing increases. Autoantibody profiles also showed differences according to immune-related adverse event (irAE) type, with rash generally featuring increases and liver toxicity demonstrating decreases. We conclude that dynamic autoantibody profiles may differ according to ICI category and irAE type. These findings may have relevance to clinical monitoring and irAE treatment.