Checkpoint inhibitor therapy has emerged as a frontline immunotherapy cancer treatment, but cancer immunotherapy results in both characteristic organ-specific autoimmunity and idiosyncratic autoimmune reactions. Rheumatologists are being increasingly called upon to treat these patients with immunosuppressive therapy, such as corticosteroids and TNF inhibitors.
An ACR session, Rheumatic Immune-Related Adverse Events from Cancer Immunotherapy: Translational Biology and Clinical Implications, will cover the translational biology of checkpoints, the clinical presentation of these immune-related adverse events (IRAEs), their immunopathogenesis, and the possible treatment approaches for this patient population. The session, which also covers the rheumatologist’s specific role in managing these adverse events, takes place from 11:00 am – 12:00 pm Monday in Room W375b.
“Checkpoint inhibitor therapy of cancer is on the leading edge of cancer immunotherapy, which is now established as a major pillar of cancer treatment; however, along with it, we have an emerging and newly defined field of disorders that fall into the heading of immune-related adverse events,” said Leonard H. Calabrese, DO, FACR, Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and Vice Chair of the Department of Rheumatic and Immunologic Diseases. “Some have suggested that these autoimmune and/or autoinflammatory complications represent an Achilles heel of cancer immunotherapy.”
During the session, Dr. Calabrese will discuss the biologic underpinnings of immunologic checkpoints, including their role in immunologic exhaustion, the development of idiopathic autoimmune diseases, and their role in rheumatic immune-related adverse events.
“At the scientific level, understanding the biology of checkpoints will not only help us manage and hopefully prevent these IRAEs, but also provide insight into the pathogenesis of autoimmune diseases, including conditions such as rheumatoid arthritis, vasculitis, and other disorders,” Dr. Calabrese said.
On the clinical forefront, he said that the rheumatic complications of cancer immunotherapy, while not among the most common, can be particularly severe and have the potential to result in chronic disease, which is unique among the spectrum of IRAEs. Additionally, he noted, as these cancer drugs have moved from academic centers into the community, the incidence of related complications is increasing, meaning that rheumatologists will be seeing more of these patients in their practices.
“Rheumatologists need to engage in robust education in this new area of disease. We need to be aware of the potential complications, we need to be able to recognize and diagnose them, and we need to participate in their management,” he said. “Rheumatologists have a unique role to play in diagnosing and treating IRAEs because of our expertise in the management of multi-system autoimmune diseases.”
Moving forward, Dr. Calabrese said, more research is needed in order to understand the mechanisms at work in rheumatic IRAEs.
“We know very little, for example, about the use of checkpoint inhibitors in patients with preexisting autoimmune diseases in general and rheumatic diseases specifically, so this is an area of need,” he said. “We need biomarkers to identify patients who are at risk and we also need to understand the ramifications of treating these complications and whether that will compromise the antitumoral effects of checkpoint inhibitors. There is a lot out there that is still unanswered.”