Background/Purpose: The strategy of using monoclonal antibodies to inhibit checkpoints on T cells, and enhance T-cell activity against cancer cells has significantly improved the survival of patients with advanced malignancies, particularly using inhibitors of the checkpoints PD-1 and CTLA-4. Treatment can be complicated by inflammatory and immune-related adverse events (irAE). This large case series reports on eighteen patients’ treated with checkpoint inhibitors at three sites in Sydney, Australia and the rheumatic irAE noted. The purpose of the case series is to add the Australian experience into the mix of this emerging clinical entity.

Methods: This study included 18 patients with advanced cancer (15 melanoma, 2 non-small cell lung cancer, 1 renal cell carcinoma) treated at Melanoma Institute Australia, Westmead Hospital or Royal North Shore Hospital, who were referred for rheumatological evaluation from 2013 to 2016. Data was collected retrospectively by medical chart review and examined for the nature of symptoms, time to onset of symptoms, duration of immunotherapy prior to onset of rheumatic irAE, management strategies and treatment outcomes.

Results: The patient characteristics, immunotherapy regimes and presentations are summarised in Table 1 below. Joints affected were mainly large joints associated with tenosynovitis and peri-articular symptoms. Time to onset of symptoms was variable. There were no sex differences. All of these patients had a negative rheumatoid factor (RF) and anti- cyclic citrullinated protein (anti-CCP) antibody. Most patients responded to NSAIDs or low dose prednisone and were able to remain on immunotherapy for their malignancy.

Conclusion: Immunotherapy has an important role in the treatment of advanced malignancies. In our study the rheumatic irAEs appear, in the majority, to be easily managed and patients can remain on treatment with their check point inhibitor. The underlying cause and pathogenesis of these adverse effects remains unknown. Interestingly, the grading systems or guidelines for classification of rheumatic irAEs are much less established than those for gastrointestinal or endocrine manifestations. There is limited experience in the management of rheumatic irAEs and no consensus guidelines on how best to manage these rheumatic irAEs. Progress is required on how to best classify, evaluate, stratify and manage these conditions.

Table 1: Patient characteristics, immunotherapy and presentation

* Some patients presented with more than 1 irAE

** Some patients had more than 1 radiological finding, some patients had no radiology completed

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/musculoskeletal-immune-related-adverse-events-with-use-of-checkpoint-inhibitors-in-malignancy-experience-in-sydney-australia/