Background/Purpose: The new and emerging field of immune related adverse events (irAEs) from cancer immunotherapies presents many unanswered questions. The spectrum of irAEs is broad and the underlying pathophysiology, natural history, and relationships among many of these complications is incompletely understood. Most commonly encountered irAEs (skin, gut, liver) tend to be either self-limited or resolve with immunosuppressive therapy. Others, such as some endocrine irAEs, do not resolve and may represent end-organ damage rather than ongoing auto-inflammation. Rheumatic irAEs are among the least understood and their natural history has not been previously described. In our early experience we observed that many rheumatic irAEs are persistent. It is the purpose of this study to report on the expanding clinical spectrum of irAEs observed in our clinic and describe the natural history of rheumatic irAEs.

Methods: Beginning in February 2016 an interdisciplinary group was created to manage irAEs. Patients were identified by the treating oncologist and triaged by a designated advanced practitioner with assistance from a registered nurse. Each patient was seen by one of two designated rheumatologists. A detailed review of the EMR was performed including demographics, malignancy details, checkpoint inhibitor (drug(s), date started, date of last dose), pre-existing autoimmune history, nosology of irAE (type, date of onset, diagnostic testing), autoimmune serology. Information was also obtained regarding duration of follow up, status of malignancy, relationship of rheumatic irAEs to other irAEs and to establish chronology and duration of irAEs.

Results: irAEs were evaluated in 21 patients including 18 patients without and 3 with pre-existing autoimmune disease. 10 patients received anti- CTLA-4 or anti-PD-1/PD-L1 monotherapy and 11 received them in combination. Of the de novo irAEs, we observed 12 cases of inflammatory arthritis, 4 sicca, 4 PMR-like syndromes and 1 myositis. Immunotherapy was interrupted based on rheumatic irAEs in 12/18 patients and for endocrine irAEs in 3. Median time between first dose and onset of rheumatic irAE was 16 weeks (range 1.7-213). Median time between onset of rheumatic irAE and last follow up was 61 weeks (range 15.1-153). At follow up only 4/18 patients were able to discontinue rheumatic irAE treatment. 7 patients were stable on irAE treatment. 7 were symptomatic despite escalating therapy. During the course of managing irAEs 17/18 patients received glucocorticoids for rheumatic irAE (prednisone 15-60mg), 5/18 (28%) received at least one bDMARD and 2/18 (11%) at least 2 bDMARDs.

Conclusion: These data further our understanding of the expanding spectrum of rheumatic irAEs and add new observations on their natural history with particular attention to chronology of onset, duration and relationship to intercurrent irAEs affecting other organ systems. Our data further suggest that rheumatic irAEs are not self-limiting, may require prolonged immunosuppressive therapy, occasionally with biologics, and often may lead to permanent cessation of immunotherapy. This has important ramifications for rheumatologists, who will continue to see an ever-growing number of patients with rheumatic irAEs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rheumatic-immune-related-adverse-events-from-checkpoint-inhibitor-therapy-for-cancer-long-term-follow-up-data/