Managing adverse events from checkpoint inhibitors in a ‘data-free zone’
SAN DIEGO — Increasing use of checkpoint inhibitors in cancer therapy is leading to an uptick in immune-related adverse events for rheumatologists to manage, according to a presentation at the Congress of Clinical Rheumatology West.
Jeffrey Sparks, MD, assistant professor of medicine in the division of rheumatology, immunology and allergy in the Department of Medicine at Brigham and Women’s Hospital,
described the current state of affairs in immune-related adverse events (irAEs) as a “data-free zone,” largely because physicians have cases series, and not randomized controlled trials, to draw from in guiding treatment decisions. “There is a lot of heterogeneity in the data, which makes it difficult to understand what is going on,” he said. “Any organ can be involved in these events.”
Sparks was quick to note that while irAEs previously might have given oncologists pause in using immune checkpoint inhibitors, attitudes are changing. “It used to be that oncologists were conservative about using them, particularly in patients who had previous signs of autoimmune disease,” he said. “That is changing because of their known efficacy, and because patients are demanding them. This is going to complicate things for physicians managing these patients.”
Pneumonitis, colitis, myocarditis, uveitis, vasculitis, inflammatory arthritis, polymyalgia rheumatica, myopathy and sicca syndrome are just some of the events that have been tied to immune checkpoint inhibitors. “We are getting to the point where we are going to have to go beyond the case series to understand all of these events,” Sparks said, but he believes that more data will be emerging in the coming months and years. “Those data will obviously be quite helpful, but this is still a highly evolving field.”
That said, Sparks offered suggestions on how to manage these patients. In general terms, he suggested starting with glucocorticoids, followed by DMARDs, then biologics as necessary. “It is important to talk to patients about pre-existing autoimmune diseases,” he said. “A lot of the data I am using are anecdotal, and I often have to consider the oncologists’ willingness to use these medications. I still do not have a clear sense of what is working and what is not.”
Mycophenolate mofetil and rituximab (Rituxan; Genentech, Biogen) also may have utility, along with IL-6 and IL-17 inhibitors. “But this information may not help a whole lot, because the list essentially includes our entire armamentarium,” Sparks said.
Addressing specific treatments for specific diseases, Sparks noted that steroid monotherapy may be sufficient for patients with inflammatory arthritis. DMARDs may also have utility in these patients. “At the moment, it is going to be a negotiation with the oncologist,” he said.
For Sicca syndrome, the mouth-related symptoms can be “quite debilitating,” according to Sparks. “Steroids are often needed.”
While he had few treatment suggestions for myopathy, Sparks noted that rheumatologists should be on the lookout for a very sudden onset of generalized pain. “Patients feel like they have been hit by a truck,” he said. “This is becoming a very common irAE with immune checkpoint inhibitors.”
As a parting note, Sparks underscored the necessity of managing these patients in a team approach with oncology. “This is a tremendous opportunity for us as a specialty to build collaborations,” he said. “The majority of these patients will have to be managed without abandoning immune checkpoint inhibitors.” —by Rob Volansky
Sparks J. Rheumatologic manifestations presenting from checkpoint inhibitors. Presented at: Congress of Clinical Rheumatology West. September 26-29, 2019; San Diego.
Disclosure: Sparks reports receiving research support to Brigham and Women’s Hospital from the National Institutes of Health, Rheumatology Research Foundation, Amgen, and Bristol-Myers Squibb; and consulting for Gilead, Janssen and Optum.