Distinct autoantibody profiles across checkpoint inhibitor types and toxicities

Hong Mu-Mosley, Mitchell S. von Itzstein, Farjana Fattah, Jialiang Liu, Chengsong Zhu, Yang Xie, Edward K. Wakeland, Jason Y. Park, Brad S. Kahl, Catherine S. Diefenbach, David E. Gerber

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number2351255
JournalOncoImmunology
Volume13
Issue number1
DOIs
StatePublished - 2024

Keywords

  • Autoantibodies
  • biomarkers
  • CTLA-4
  • immune checkpoint inhibitor
  • immune-related adverse events
  • immunotherapy
  • PD-1

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