Immune-related adverse events present ‘double-edged sword,’ need multidisciplinary input
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Although oncologists take the lead in cancer management with immunotherapies, rheumatologist input is essential to managing the ensuing immune-related adverse events, which pose challenges to coordinated patient care.
“The most fascinating thing about immune-related AEs in cancer treatment is that you have a better prognosis if you have an immune-related AE,” Alexa Meara, MD, associate professor of internal medicine at the Ohio State University Wexner Medical Center, said in her presentation at the 2022 Association of Women in Rheumatology National Conference. “You survive longer.”
This “double-edged sword” is just one of the many unexplained phenomena associated with this particular set of medical challenges.
Conventional wisdom at the moment is that 30% of cancer patients undergoing immune therapy will experience a brief flare of an immune-related event, 30% will acquire a new chronic autoimmune disease and 30% will have no events. “Our understanding of irAEs continues to evolve,” Meara said.
Another unanswered question pertains to whether an irAE can become a permanent autoimmune disease. Meara said that the answer is, “Yes,” but that the frequency of this occurrence is unknown. “Some of it is transient, some is not,” she said.
Experts in the irAE area are also uncertain when immune therapies can be stopped and restarted, according to Meara. “None of that work has been done,” she said.
There has been some research conducted in biomarkers that could predict response to immune therapies and the likelihood of irAEs, but Meara noted that the data are not “precise” as yet.
Regarding the seriousness of adverse events, Meara suggested that while clinical trialists differentiate between grade 1, 2 or 3-4 events, oncologists generally speak of them more in pass/fail terms. “It’s like pregnancy,” she said. “You either have hyperthyroid or you don’t. You have adrenal insufficiency or you don’t.”
That said, clinicians should be on the lookout for the most concerning patients. “Serious events do occur, probably more frequently than in clinical trials,” Meara said.
Regarding treatment for irAEs, Meara noted that steroids have become one of the mainstays. However, she acknowledged the adverse event profile associated with prednisone and that tapering is necessary to minimize the duration of exposure. “A little bit of steroid in these patients to maintain immunotherapy can go a long way,” she said.
Hydroxychloroquine, leflunomide, interleukin (IL)-6 inhibitors or tumor necrosis factor (TNF) inhibitors may have utility in irAEs, depending on what is causing the inflammation, according to Meara. “But we do not know the duration,” she said. “You may only need to use these drugs for a short period and then wean them off.”
Oncologists have also used janus kinase (JAK) inhibitors in these patients. For clinicians who may have concerns about the black box warnings associated with this class of drugs, Meara offered a counterpoint. “If you are only giving them for a month, does that black box warning really matter?” she said.
There are guidelines on the topic of irAEs from the National Comprehensive Cancer Network that go through various disease states and treatments pertaining to the topic of irAEs, but Meara stressed that the manual is based on “minimal evidence.”
Despite the fact that so little is known about these events, Meara offered some practical advice for rheumatologists to consider. One point is that while rheumatologists can test various drugs in their patients over time, the mechanism of action and pharmacology of the drugs involved in cancer treatment “really matter” because of the importance of the anti-tumor effect. The implication was that every effort should be made to find the right treatment immediately when a patient has an irAE, rather than cycling through several classes.
She added that irAEs will likely confound hematologists/oncologists and rheumatologists for some time. “These diseases are not going to go away,” she said. “They are going to mimic our other diseases.”
This will lead to questions, and perhaps second guessing, from the treating physicians, Meara noted. “Did the drug do it or did I do it? Did I not treat them enough?” she said. “Partnering with oncology is going to be a big deal.”
But Meara was clear that rheumatologists can bring a lot to the table in these clinical situations. “Rheumatologists need to understand that oncology is going to be at the center of treating these patients,” she said, noting that cancer management breeds a kind of “tunnel vision” where the cancer is the most important target.
“But what we as rheumatologists can do is care for the patient holistically,” she said.
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