Because rheumatic disease therapies tamp down immune responses, the question, Dr. Cappelli said, is, “What happens when the forces of immune activation outweigh those of inhibition? … Unfortunately, with these immune checkpoint inhibitors, there’s no free lunch.”
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Explore This IssueMarch 2018
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ICIs can cause a wide array of immune-related adverse events (irAEs), affecting all body systems. Such events can range in severity and in timing, but combination ICI treatment tends to lead to more common events of all types, Dr. Cappelli said.
In a systematic review published in 2016, the four most common irAEs were found to be inflammatory arthritis, sicca syndrome, polymyalgia rheumatica and giant cell arteritis (PMR/GCA), and myositis.3
A guideline for how to handle inflammatory arthritis that emerges with ICI therapy was published last year. Its authors suggested that in the mildest cases, physicians should continue the immunotherapy, with NSAIDs and consideration of prednisone or intra-articular steroids. For moderate cases, they also suggest continuing immunotherapy at first, but to consider holding it if there’s no response to oral prednisone after at least four weeks. In severe cases, they suggest holding immunotherapy, trying oral prednisone for four weeks, and then considering TNF inhibitors or methotrexate.
Sicca is treated with saliva substitutes, sialogogues, artificial tears and other therapies. In PMR/GCA, Dr. Cappelli said, inflammatory markers are almost always elevated, with corticosteroids the mainstay treatment. And in myositis, ICIs are held or stopped in almost all cases, with corticosteroids as the standard treatment.
‘What happens when the forces of immune activation outweigh those of inhibition?’ —Dr. Cappelli
Can Immunosuppression Affect Cancer Treatment?
Dr. Cappelli said rheumatologists and oncologists have concerns about giving immunosuppression to treat irAEs.
“[The] first, and I think the foremost, worry is, are we abrogating the anti-tumor effect of the immune checkpoint inhibitors? Are we impairing natural tumor defenses, and are there overlapping side effects?” she said. “Ultimately, it’s a multidisciplinary discussion to decide on treatment because there’s limited data in the published literature.”
Can patients with autoimmune disorders who develop cancer be treated with ICIs? Patients with rheumatic diseases were excluded from the original clinical trials, so there’s not much data to go on, she said.
One case series found eight of 30 melanoma patients with a variety of rheumatic conditions had an exacerbation of the underlying illness, with most managed with steroids but with two inflammatory bowel disease patients needing infliximab. In another case series, 20 of 52 melanoma patients had a flare of their autoimmune condition that required immunosuppression, and two discontinued their ICI because of the flare.