Peter A. Merkel
CHICAGO — Rheumatologists, as well as the rheumatology specialty as a whole, must become more aware of, and develop treatments and guidelines for, the problem of rheumatologic side effects related to checkpoint inhibitor therapy, according to Peter A. Merkel, MD, MPH, of the University of Pennsylvania.
“We have new rheumatic diseases that we have to know about that we are treating, and that we have to get directly engaged in, and that is the connection between checkpoint inhibitors and rheumatic diseases,” Merkel said, addressing attendees at the ACR/ARHP 2018 Annual Meeting. “This new class of drugs, which has become critical for patients with a variety of solid organ and other malignancies, is intriguing.”
Checkpoint inhibitors, which include anti-CTLA-4, anti-PD-1 and anti-PD-L1 agents, have since 2011 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.
However, throughout 2017 and 2018, there has been an “absolute cascade” of publications detailing new or exacerbated cases of rheumatic disease associated with the use of these therapies, Merkel said.
According to Merkel, the weight of the clinical evidence is growing increasingly clear that such exacerbation is linked to the use of checkpoint inhibitors, even sometimes in patients who had been in remission. In addition, the therapies have been linked to new rheumatic disease, including inflammatory arthritis, lupus and “lupus-like” conditions, he said.
Patients using checkpoint inhibitors for cancer have also demonstrated side effects related to myositis, sarcoidosis, Sjögren’s syndrome, vasculitis and other diseases, according to Merkel.
However, the answer to this development cannot include simply ceasing these treatments, as they have become a life-saver for many patients with cancer, he added.
“Our field must jump into this, scientifically and clinically,” Merkel said. “I know at our center we are having initiatives in which our immunologists and some of our rheumatologists are working with our oncologists to form collaborations to study clinically and scientifically what is happening here. This is an amazing, somewhat natural experiment we are doing — we are fundamentally changing the immune system, and its effect on immune-related diseases is fascinating. However, importantly, our patients are suffering. I can’t give you the magic answer for treating them, but I think we will learn that if we team up to study this.” – by Jason Laday
Disclosure: Merkel reports consulting fees from AbbVie, Boehringer-Ingelheim, Bristol-Myers Squibb, and Celgene and others; and research support from AbbVie, Biogen, Bristol-Myers Squibb, Celgene, ChemoCentryx, Genentech/Roche and others.
Merkel PA. “Year in Review: Clinical Rheumatology.” Presented at ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.