ATLANTA—One of the hottest topics in medicine is the emerging field of cancer immunotherapy. However, immune-related adverse events (irAEs) are associated with the therapy, and when things go wrong, they can go very, very wrong, said Ryan Sullivan, MD, during the 2019 ACR/ARP Annual Meeting in November.
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“The guiding principle of cancer immunotherapy is [that] an individual’s cancer can be eradicated if the immune system can be instructed to do so.” But, Dr. Sullivan says, “While [the drugs are] helping many patients—some with durable responses—there often is a catch.”
Part of the allure of the therapy is cancer cells’ behavior: Every cancer that has been diagnosed has figured out how to defend itself against the immune system. Dr. Sullivan explained that immune checkpoint inhibitors “take the brakes off” immune system cells, including T cells that keep immune system responses in check, allowing them to kill cancer cells. “The problem is we’re taking away the regulators of the immune system, so it’s like we’re playing with fire, resulting in irAEs that can range from minor to major. So a problem that might mirror rheumatoid arthritis or ulcerative colitis becomes a much more significant problem because you’ve taken away the regulators,” he said.
Dr. Sullivan is board certified in medical oncology and an attending physician in the Division of Hematology/Oncology at Massachusetts General Hospital, Boston. He, along with Jeffrey S. Weber, MD, PhD, deputy director of the Laura and Isaac Perlmutter Cancer Center and professor of medicine at the New York University School of Medicine, and Elad Sharon, MD, MPH, from the National Cancer Institute Cancer Therapy Evaluation Program (CTEP), Bethesda, Md., were the joint presenters of this Basic Science Session.
The emerging central challenge of cancer immunotherapy is uncoupling the anti-tumor response from anti-patient immune activation, or the autoimmunity that comes with generating effective immune responses. “Many of these immune-related adverse events are auto-inflammatory, and as rheumatologists, you might think they’re very similar to things you see in your practice,” said Dr. Weber. “They’re not exactly the same, especially the ones related to [the gastrointestinal] and endocrine [systems].”
Dr. Sullivan said a great deal of progress is being made to understand and solve irAE issues. “The good news is medical oncologists are becoming more and more familiar with these problems and solving them.”
At Mass General, Dr. Sullivan said, they’re treating more and more patients with checkpoint inhibitors because there are more and more indications to do so. “The number of irAEs [related to checkpoint inhibitor use], which went up between 2011 and 2017, is now leveling off—even as the number of patients increases.”