Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Abstract
Immune checkpoint inhibitors (ICIs) are newly approved treatments for advanced malignancies that are increasing survival. The mechanism of these drugs, non-specifically activating T cells, also leads to immune-mediated damage of tissue or immune-related adverse events (IRAE). IRAEs with rheumatic phenotypes are increasingly being recognised. Inflammatory arthritis, sicca syndrome, inflammatory myopathy, vasculitis and lupus nephritis have been described as a result of ICIs. Use of ICIs will be expanding in the coming years for several reasons. ICIs will be used in earlier stage cancer, for more indications, and additional drugs will be approved. The rheumatologist plays a critical role in evaluating and treating these patients. The expertise of rheumatologists in evaluating rheumatic signs and symptoms and treating patients with immunosuppression are critical in ensuring the optimal outcomes for patients with rheumatic IRAE. Collaboration between oncology and rheumatology for clinical care and research will enhance understanding of these new disease entities.

https://www.ncbi.nlm.nih.gov/m/pubmed/27752360/

Why the rheumatologist matters

Rheumatologists have a unique role to play in managing IRAE. Patients with rheumatic IRAE differ from patients with traditional rheumatic disease in several important ways. First, it appears that their IRAEs do not behave identically to the corresponding classic rheumatic disease. Observations to date show a lack of the traditional autoantibodies associated with RA and Sjogren's syndrome in most patients with ICI-induced inflammatory arthritis and sicca syndrome, respectively.13 Also, the steroid requirements of therapy for control may be much higher than typically required to manage ‘classic’ inflammatory arthritis.13 Importantly, all patients with rheumatic IRAE have or recently had advanced stage cancer, so there would be concerns about using immunosuppression in them. These concerns are compounded in patients whose cancer has responded to immunotherapy with further concerns about impairing a salutary response to the malignancy with concomitant or subsequent immunosuppression.

Conclusions

Rheumatic IRAEs are likely under-reported to date, and the trend towards vast expansion in use of ICI drugs suggests that ICI-induced rheumatic disease will be an increasing problem encountered by oncologists and rheumatologists in the near future and over time. Increased awareness of the potential for an array of rheumatic IRAEs is critical to early recognition, evaluation and therapy, which will hopefully foster better long-term outcomes. Careful tracking of patients treated with ICIs with a registry would provide more comprehensive epidemiologic data for rheumatic and other IRAEs. The expertise of rheumatologists will be critical to successful management of patients with ICI-induced rheumatic disease, particularly in the use of biologics and immunosuppressant/immunomodulatory medications in general. Collaboration with oncology to research the pathogenesis of rheumatic IRAE and to define appropriate treatment algorithms will lead to better understanding of this growing phenomenon and identify potential targets for treatment.

Cancer immunotherapy-induced rheumatic diseases emerge as new clinical entities.
Cappelli LC, et al. RMD Open. 2016.
Authors
Cappelli LC1, Shah AA1, Bingham CO 3rd1.
Author information
1
Department of Medicine, Division of Rheumatology , Johns Hopkins University , Baltimore, Maryland , USA.
Citation
RMD Open. 2016 Sep 28;2(2):e000321. eCollection 2016.

Key messages

What is already known about this subject?

Immune related adverse events from immune checkpoint inhibitors used to treat cancer can resemble classic rheumatic diseases.

How might this impact on clinical practice?

Rheumatologists have an important role to play in the clinical care and research of immune related adverse events.