Rheumatic adverse effects of checkpoint inhibitor therapy chronic in 50% of patients
BOSTON — The potential rheumatic side effects of checkpoint inhibitor therapy in patients with cancer can include arthralgia, arthritis, polymyalgia rheumatica, giant cell arteritis, myositis, sicca syndrome and systemic lupus erythematosus, and can be chronic in approximately 50% of patients, according to findings presented here.
During a presentation at the 2018 Interdisciplinary Autoimmune Summit, Leonard H. Calabrese, DO, vice chairman of rheumatic and immunologic disease at the Cleveland Clinic, said rheumatic complications are among the most poorly defined immune-related adverse effects associated with anti-PD-1 and other checkpoint therapies, with a prevalence of 5%.
“What is really interesting about the rheumatic complications [of checkpoint therapy] – and this has been found in numerous centers – is that particularly inflammatory polyarthritis is chronic in up to 50% of patients,” he said. “No other immune-related adverse effect in any other organ system has a chronic inflammatory phase, that we are aware of. In other words, it appears that even short-lived exposure to checkpoint inhibitors may actually induce or unmask an inflammatory disease.”
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 rheumatologists, but also specialists of virtually every kind, as well as hospitalists, internists and family physicians.
Some current theories regarding the mechanisms underlying immune-related adverse events in checkpoint therapy include the reinvigoration of T cells, increased cytokines and other factors. However, Calabrese noted that an issue with these theories is that although nearly all patients reinvigorate, only a small percentage develop these “peculiar and severe” adverse events.
When severe, rheumatic complications from checkpoint therapy require often-high doses of glucocorticoids – ranging from 0.5 to 1 mg/kg per day, Calabrese said. However, he added there are currently no “set rules” or “secret sauce” for managing these side effects. He later suggested rheumatologists treat adverse effects related to checkpoint therapy with what is required to control them.
According to Calabrese, guidelines for managing these toxicities for rheumatic diseases have been recently released from the Society for Immunotherapy of Cancer. The guidelines include rigorous diagnostic evaluations based on early recognition and ruling out other causes, which can include infections related to chemotherapy or glucocorticoids, complications of progressive malignancy and primary forms of autoimmune, infectious or infiltrative disease. Treatment in the guidelines range from symptomatic therapy, to glucocorticoids, to withholding immune checkpoint inhibitors to, in severe cases, advanced immunosuppression.
“We do not consider this a contraindication, but we follow them in our institutions as rheumatologists, as quarterbacks of this, before they institute the checkpoint therapy,” Calabrese said. “It is a work in progress.” – by Jason Laday
Calabrese LH. Management of Rheumatologic Side Effects of Anti-PD-1 Therapy. Presented at: IAS 2018; April 27-29, 2018; Boston.
Disclosure: Calabrese reports he is a consultant for AbbVie, Amgen, BMS, Crescendo, Genentech, GSK, Janssen, UCB, Pfizer and Regeneron.