Background/Purpose: Immune checkpoint inhibitors (ICI) targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) and its ligand PD-L1 have had substantial success in treating a variety of cancers. However, immune-related adverse events (irAEs) do occur and can cause significant morbidity and mortality. Although autoimmune (AI) processes share features of irAEs, little research has been done regarding the association between AI serologies and the risk of irAEs. The objective of our review is to determine whether positive AI antibodies (with or without presence of rheumatologic disease) were associated with irAEs and to characterize the nature, severity, and consequences of these irAEs.

Methods: We retrospectively evaluated charts of patients (pts) treated with ICIs at the Ohio State University Comprehensive Cancer Center between 2009 and 2017 under an IRB approved protocol. Those who had known rheumatic antibody testing associated with common rheumatic pathologies before, during or after treatment with ICI were identified. We collected information on pt demographics, clinical and treatment history, and test results to identify exacerbations of existing rheumatologic disease and irAE events. See table 1.

Results:

A total of 15 patients were included in this study and received the CTLA-4 inhibitor ipilimumab (lpi) or anti-PD-1 treatment with nivolumab (nivo) or pembrolizumab (see Table 1). Many were positive for more than one auto-Ab during their treatment course. Twelve pts (80%) had an irAE after a median of 3 cycles and 58% of those patients had documented evidence of positive antibodies prior to the onset of toxicity. Treatment included NSAIDs, steroids, treatment delay, and treatment cessation. Only 4 patients had pre-existing rheumatic diseases; several developed AI irAEs (often multiple) including: arthralgias, hypophysitis, Hashimoto’s, and colitis. The pre-existing rheumatic disease patients with melanoma on Ipi had flares of their disease requiring steroids and/or cessation of therapy. A total of 9 patients had Ab drawn before treatment with ICI: 4 positive, and 5 negative. One patient with SCC and pre-existing Lupus suffered respiratory failure and died. None of 5 patients with negative ab had known rheum disease and 4 out of these 5 patients did not have complications. See table 1.

Conclusion: This study adds to the current knowledge about pts with pre-existing rheumatic disease who are treated with ICI. In our study all 4 pts with prior rheum disease developed complications related to treatment.. The role of routine testing for rheumatologic antibodies in unselected patients remains unclear, however close surveillance of patients with pre-existing disease is certainly warranted. Whether a specific profile or pattern of autoantibodies may be useful in the diagnosis and evaluation of suspected irAE remains an area of active investigation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immune-check-point-inhibitors-auto-antibodies-and-immune-adverse-reactions/