EULAR: Rheumatologist, oncologist collaboration 'pivotal' to enhance checkpoint inhibitor management
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Oncologists should be encouraged to promptly consult with rheumatologists in the event of suspected immune-related adverse events due to checkpoint inhibitor therapy, according to a series of “points to consider” published by EULAR in the Annals of the Rheumatic Diseases.
“There is a growing enthusiasm for the rheumatic immune-related adverse events amongst rheumatologists, but a lack of evidence describing the optimal management of patients experiencing such toxicity while allowing effective antitumoral therapy to continue,” Marie Kostine, MD, of the Bordeaux University Hospital, in France, told Healio Rheumatology.
“Moreover, when we started this project in 2018, a recent survey revealed that a large proportion of rheumatologists have limited experience and lacked confidence in clinically addressing rheumatic irAEs, highlighting the need for education and recommendations on this emerging topic,” she added. “Therefore, we consider this project to be timely and worthy of endorsement by EULAR.”
To bring together expert opinions regarding the identification and management of immune-related adverse events among patients with cancer receiving checkpoint inhibitors, EULAR formed an international task force. Members included 19 clinical experts from Europe and North America — of whom 14 were rheumatologists, with two internists and three oncologists — one clinical epidemiologist, one allied health professional and two patient representatives.
The group met in 2018, in Zürich, Switzerland, to developed research questions for a systematic literature review. They later met again in January 2019 to present the results of the literature search, and, using a consensus procedure, produced and approved a series overarching principles and “points to consider.”
In all, the task force developed and approved four overarching principles and 10 points to consider. Among the overarching principles is a call for shared decision-making between patients, oncologists and rheumatologists. Meanwhile, the 10 “points” inform rheumatologists on the wide variety of musculoskeletal immune-related adverse events that fall short of the usual classification criteria for rheumatic diseases, as well as their differential diagnoses. Further, the task force recommends early referral and access to rheumatologists, to help document the target organ inflammation.
The task force also detailed three treatment escalations to consider:
- Local or systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, subsequently tapered to the lowest efficient dose;
- Conventional synthetic DMARDs in the event of an inadequate response to glucocorticoids or for steroid sparing; and
- Biological DMARDs for severe or refractory adverse events.
Members of the task force also included a warning regarding severe myositis requiring high dose of glucocorticoids and close monitoring. In addition, patients with pre-existing rheumatic disease should be kept at the lowest efficient baseline immunosuppressive regimen before beginning immunotherapies.
“These statements aimed to raise awareness and to assist rheumatologists to improve the diagnosis and the management of patients with irAEs,” Kostine said. “They are based almost entirely on low levels of evidence and on experts’ opinion. As new data emerge from different groups, they will undoubtedly require updating over the next few years. This international project was the first step of an emerging and exciting topic and highlighted a busy research agenda.”
“Notably, since optimal treatment strategies are not defined yet, we need to better understand pathophysiology of rheumatic irAEs, to provide insights into possible targeted therapies with glucocorticoid saving approaches,” she added. “We also need to validate these recommendations in longitudinal cohorts and/or dedicated clinical studies.”
Perspective
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Kamran Chaudhary, MD
Increasing utilization of monoclonal antibodies or checkpoint inhibitors targeting the CTLA-4 and PD(L)-1 receptors has advanced the treatment landscape for a variety of malignancies leading to better outcomes and survival. However, the resultant immune system activation of T-cells that possess anti-tumor activity have led to the emergence of immune-related adverse events (irAEs) that include a wide spectrum of rheumatic conditions. Rheumatologic prevalence of irAEs may be as high as 22% and early recognition and management is important for optimization of patient outcomes.
Given that rheumatic irAEs are increasingly being recognized and reported along with the increased use of checkpoint inhibitors and the limited experience rheumatologists may have in assessing and managing patients with irAEs, a EULAR task force set out to provide a consensus to address this issue through a systematic literature review. The result of this process includes four overarching principles and 10 points for consideration that address the role of rheumatologists in caring for these patients and the wide range of possible diagnostic and management considerations.
These recommendations serve as a framework to increase awareness among rheumatologists and guide them in being able to recognize, assess and comanage patients with rheumatic irAEs. In addition, given the difficulty of obtaining a timely rheumatological evaluation, these recommendations should help clinics prioritize patients to be evaluated when rheumatic irAEs are suspected in order to optimize patient outcomes and engage early in a shared decision-making process in conjunction with the oncologist and the patient.
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