Distinct autoantibody profiles across checkpoint inhibitor types and toxicities.

in Oncoimmunology by 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

TLDR

  • The study investigates how different immune checkpoint inhibitors (ICI) affect circulating autoantibodies in patients with Hodgkin Lymphoma. The study compares autoantibody levels at Cycle 2 Day 1 (C2D1) to pre-treatment baseline and identifies significant differences in the results between the ipilimumab-containing regimens and the nivolumab arm, with the former generally showing increases in autoantibody levels and the latter showing decreases. The study also highlights the differences in autoantibody profiles according to irAE type, with rash generally featuring increases and liver toxicity demonstrating decreases. The study suggests that dynamic autoantibody profiles may differ according to ICI category and irAE type, which may have relevance to clinical monitoring and irAE treatment. The study identifies limitations, such as the small sample size and the need for further validation of the findings. Future research should address these limitations and explore the potential of dynamic autoantibody profiles in larger studies and clinical settings.

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.

Overview

  • The study investigates the effects of different immune checkpoint inhibitors (ICI) categories on circulating autoantibodies in patients with Hodgkin Lymphoma enrolled in the E4412 trial. The study compares autoantibody levels at Cycle 2 Day 1 (C2D1) to pre-treatment baseline and observes generally increases in ipilimumab-containing regimens, with decreases noted in the nivolumab arm. The study also identifies differences in autoantibody profiles according to immune-related adverse event (irAE) type, with rash generally featuring increases and liver toxicity demonstrating decreases. The study aims to understand the effects of different ICI categories on circulating autoantibodies in patients with Hodgkin Lymphoma and their potential relevance to clinical monitoring and irAE treatment. The hypothesis being tested is that different ICI categories may have different effects on circulating autoantibodies in patients with Hodgkin Lymphoma.

Comparative Analysis & Findings

  • The study compares autoantibody levels at Cycle 2 Day 1 (C2D1) to pre-treatment baseline and observes generally 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. The study identifies significant differences in the results between the ipilimumab-containing regimens and the nivolumab arm, with the former generally showing increases in autoantibody levels and the latter showing decreases. The study also highlights the differences in autoantibody profiles according to irAE type, with rash generally featuring increases and liver toxicity demonstrating decreases. These findings suggest that dynamic autoantibody profiles may differ according to ICI category and irAE type, which may have relevance to clinical monitoring and irAE treatment.

Implications and Future Directions

  • The study's findings suggest that dynamic autoantibody profiles may differ according to ICI category and irAE type, which may have relevance to clinical monitoring and irAE treatment. The study identifies significant differences in the results between the ipilimumab-containing regimens and the nivolumab arm, with the former generally showing increases in autoantibody levels and the latter showing decreases. The study also highlights the differences in autoantibody profiles according to irAE type, with rash generally featuring increases and liver toxicity demonstrating decreases. These findings suggest that future research should explore the potential of dynamic autoantibody profiles as a tool for clinical monitoring and irAE treatment. The study also identifies limitations, such as the small sample size and the need for further validation of the findings. Future research should address these limitations and explore the potential of dynamic autoantibody profiles in larger studies and clinical settings.
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