Leonard H. Calabrese
CLEVELAND — Interdisciplinary management of immune-related adverse events associated with checkpoint inhibitors, with collaboration between rheumatologists and oncologists, represents the ideal paradigm for interdisciplinary patient management, noted Leonard H. Calabrese, DO, chairman of clinical immunology at the Cleveland Clinic’s department of rheumatic and immunologic disease.
“For the rheumatologists, we now see patients routinely from the oncologists, saying ‘This patient has rheumatoid arthritis,’ ‘This patient has scleroderma,’ ‘We want to give them checkpoint inhibitors — what do you think?’ ‘What are the risks? How shall we do this together?’” Calabrese said, addressing attendees at the Biologic Therapies Summit. “That is the way we want to see these patients.”
“This is the quintessential interprofessional area,” he added. “Most major centers now are approaching these in a collaborative venture.”
Interdisciplinary management of immune-related adverse events associated with checkpoint inhibitors, with collaboration between rheumatologists and oncologists, represents the ideal paradigm for interdisciplinary patient management, according to Calabrese.
Since 2011, checkpoint inhibitors, including anti-CTLA-4, anti-PD-1 and anti-PD-L1 agents have been approved by the FDA for the treatment of melanoma, Hodgkin lymphoma, renal cell carcinoma, non-small cell lung cancer, urothelial carcinoma and Merkel cell carcinoma. According to Calabrese, their increased use has implications not only for rheumatologists, but for specialists of virtually every kind, as well as hospitalists, internists and family physicians.
Immune-related adverse effects (irAEs) that have been associated with checkpoint inhibitors include arthralgia, arthritis, polymyalgia rheumatica, giant cell arteritis, myositis, sicca syndrome and systemic lupus erythematosus. Their incidence, for anti-CTLA-4 and anti-PD-1, is dose dependent, and they may occur as a single condition or in combination. These adverse side effects have proved fatal in 0.6% of cases, Calabrese said. Additionally, some immune-related adverse events are drug or tumor-lineage dependent.
Guidelines for managing toxicities for rheumatic diseases, released by the Society for Immunotherapy of Cancer, call for rigorous diagnostic evaluations based on early recognition and ruling out other causes. Treatment in the guidelines range from symptomatic therapy, to glucocorticoids, to withholding immune checkpoint inhibitors to, in severe cases, advanced immunosuppression. When severe, rheumatic complications from checkpoint therapy require often-high doses of glucocorticoids – ranging from 0.5 mg/kg per day to 1 mg/kg per day.
According to Calabrese, treating these adverse events requires establishing a balance between suppressing the immune response without undoing the improvements achieved by checkpoint therapy.
“What is the yin-yang of treating irAEs? On the one side, everything the oncologists are doing is kicking up the immune response, and in the presence of irAEs we are using therapies to push it down,” Calabrese said. “We don’t want to reactivate the tumor. These are some of the burning questions we are trying to mix together.”
To help strike this balance, centers need to establish interprofessional groups of consultants and physicians of varying specialties to share their experience. The Cleveland Clinic in September 2017 developed its own “tumor board” on immune-related adverse effects caused by checkpoint therapy, which, according to data presented by Calabrese at the American College of Rheumatology 2018 Annual Meeting, helped solidify rheumatologists as valued, if not central, partners in both patient management and research.
During the Biologic Therapies Summit, Calabrese noted that the Cleveland Clinic is soon expecting to expand the reach of its tumor board overseas.
“We have the first international irAE tumor board launching in two weeks, with centers from several different continents that will be presenting patients virtually to try to increase the expertise that is going into some of this critical decision-making,” he said. “...We need robust triage systems. We think that we have a lot to offer as rheumatologists treating multisystem disease, and the future is bright and challenging.” – by Jason Laday
Calabrese L. Interdisciplinary management of irAEs. Presented at: Biologic Therapies Summit VIII; May 16-17, 2019; Cleveland, Ohio.
Disclosure: Calabrese reports consulting fees from AbbVie, Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Horizon, Janssen, Novartis, Pfizer, Regeneron, Sanofi Aventis and UCB, as well as teaching and speaking fees from AbbVie, Bristol-Myers Squibb, Crescendo, Genentech/Roche, Janssen and Novartis.