Researchers have long noted links between cancer and autoimmune rheumatic diseases, particularly with patients developing cancer and traditional rheumatic diseases together over time. Clinicians are now seeing some of those same links as novel immunotherapy treatments for cancers produce a growing volume of rheumatologic immune-mediated side effects.
“Recent data suggest that both cancer and cancer therapy could trigger the development of autoimmune rheumatic diseases in some patients,” said Ami Shah, MD, MHS, Associate Professor of Medicine and Director of Clinical and Translational Research at the Johns Hopkins Scleroderma Center. “Preliminary work in diseases like scleroderma and myositis illustrates that naturally occurring anti-tumor immune responses may lead to autoimmunity. One question is whether new oncology agents that are designed to trigger robust anti-tumor immune responses can also lead to rheumatic disease through similar mechanisms.”
Dr. Shah will open the clinical science symposium Autoimmunity & Cancer, which takes place from 12:30 – 2:00 pm on Tuesday in Room 20 D. There are more questions than answers when it comes to the clinical evaluation and management of rheumatic diseases triggered by cancer, but evidence suggests that careful cancer screening may be appropriate for at least some patients with rheumatic disease.
“We are learning that at least some of our autoimmune diseases could be triggered by underlying cancers and the immune responses that develop in response to cancer,” she said. “That may have important implications for how we screen for cancer and treat our traditional rheumatologic diseases.”
There is another distinct subset of patients in whom cancer treatment is the cause of autoimmune disease. Relatively few rheumatologists have seen these patients because cancer immunotherapy is a relatively new option in oncology. But as immunotherapy becomes more common, so will immune-related adverse events.
“A new class of cancer agents, immune checkpoint inhibitors, can cause rheumatic disease, and we have minimal guidance for either evaluation or treatment,” said Laura Cappelli, MD, MHS, Assistant Professor of Medicine at the Johns Hopkins University School of Medicine. “Some of the consequences of these new agents look like our more classic rheumatic disease, from rheumatoid arthritis to a Sjögren’s-like syndrome, vasculitis, myositis, and other inflammatory adverse events.”
For now, the field of checkpoint inhibitors is relatively limited. These agents are antibodies to programmed cell death-1 (PD-1), PD-1 ligand (PD-L1) receptors or cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4).
The most common agents with immune-mediated adverse events include nivolumab and pembrolizumab (PD-1 antibodies); atezolizumab, avelumab and durvalumab (PD-L1 receptor antibodies); and ipilimumab (CTLA-4 antibody). But a growing number of agents are being submitted for approval and additional checkpoint inhibition targets are being investigated. Rheumatologists can expect to see more inflammatory disease caused by cancer treatment.
“We all need to be more familiar with the different autoimmune syndromes that can happen as a result of cancer immunotherapy and how we approach evaluating and managing these patients,” Dr. Cappelli said. “We also need to consider the effects of checkpoint inhibitors in our patients with preexisting autoimmune disease and how we can work with oncologists to ensure that these patients have the best possible outcomes for both their cancer and their autoimmune disease.”
Oncologists may need as much education in dealing with immune-modulated events as rheumatologists, she said. Fortunately, oncologists generally recognize that no matter how much they know about cancer, they are not trained to evaluate or manage musculoskeletal problems and other rheumatic complaints. That’s where rheumatologists enter the picture.