Session 108: Immune-Related Adverse Events: Current Status of Research and Paths Forward
Elad Sharon, MD, MPH – National Cancer Institute
Chloe Villani, PhD – Massachusetts General Hospital
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Since 2011, there have been more than 80 FDA-approved indications for the use of ICI therapy in the treatment of more than 17 cancer types, as well as any tumor that has microsatellite instability and/or a high tumor mutational burden. With the expanding number of approvals, the number of patients eligible for ICI therapy is dramatically increasing. Unfortunately, the success of ICIs has been accompanied by the emergence of treatment-induced toxicities termed immune-related adverse events (irAEs), which can develop during or after treatment, impact any organ system and be lethal. irAEs have been reported in up to 90% of participants on clinical trials who received single-agent or combination ICI therapy. Importantly, roughly 10%–30% of participants develop grade ≥3 irAEs, depending on the regimen used. Management of irAEs may require hospitalization and administration of immune-suppressing agents including steroids, and ICI therapy is often interrupted or stopped due to irAEs. Given the profound clinical implications of irAEs, a better understanding of these clinical presentations is crucial to prevent their occurrence, improve treatment outcomes, and develop rigorous pathways for irAE management. In this session, we will review the current landscape of irAE efforts, including irAE-specific clinical trials and new concerns for patients who are now receiving ICIs even in the adjuvant setting. We will also provide an overview of currently most optimal management of rare toxicities and discuss available data on survivorship. Finally, we will discuss results of cutting-edge translational work being perform on patient specimens aimed at furthering our mechanistic understanding of these irAE presentations, with the ultimate goals of identifying novel predictive biomarkers and therapeutic targets.