Background/Purpose: The development of de novo inflammatory arthritis (IA) occurs in 2-4% of all patients with cancer treated with programmed cell death protein 1 (PD-1) inhibitors. (1) Prognosis remains a major concern for managing physicians, particularly given the potential for immunosuppressive medications to impact the anti-tumor response. The objective of this study is to assess the overall survival of patients with melanoma who develop anti-PD-1 associated IA.

Methods: From a database of all patients who received any PD-1 inhibitor at the Mayo Clinic Rochester, Minnesota campus between January 1st, 2011 and May 1st, 2018, we identified those with metastatic melanoma and new-onset inflammatory arthritis using diagnostic codes, search terms, and manual chart review. A Cox proportional hazard model was used to examine overall survival using R statistical software.

Results: Of the 394 patients with stage IV melanoma who received any PD-1 inhibitor, 27 (6.9%) were diagnosed with inflammatory arthritis representing a rheumatic immune-related adverse effect (Rh-irAE). Mean age upon starting anti-PD-1 therapy was 62.4 (SD=13.9) and 39% of patient were female. There were no statistically significant differences in age or sex between patients with and without IA. Average duration of anti-PD-1 therapy was 225 days (SD=279) with no significant differences between groups. IA was most often polyarticular (74%) and was treated with systemic glucocorticoids in 82% of cases for a mean duration of 210 days (SD=221). Six patients (22%) were treated with disease modifying drugs and three patients (11%) required permanent anti-PD-1 discontinuation due to severe symptoms. The development of IA correlated significantly with increased overall survival (HR 0.39, 95% CI=0.19-0.81).

Conclusion: This study shows a significant survival benefit associated with the development of anti-PD-1 associated IA in patients with metastatic melanoma. The prevalence of IA was higher than previous reports on rheumatic irAEs.

1. Richter MD, Crowson C, Kottschade LA, Finnes HD, Markovic SN, Thanarajasingam U. Rheumatic Syndromes Associated With Immune Checkpoint Inhibitors: A Single-Center Cohort of Sixty-One Patients. Arthritis Rheumatol. 2019;71(3):468-475.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/overall-survival-in-patients-with-pd-1-inhibitor-related-inflammatory-arthritis-and-metastatic-melanoma/