Background/Purpose: Patients with malignancy who develop rheumatic immune related adverse events (IRAEs) during immune checkpoint blockade (ICB) are commonly autoantibody negative. The change from chemotherapy to ICB as first-line therapy in melanoma could be important since chemotherapy causes cell death of both malignant and healthy cells, potentially increasing exposure of self-antigen. This in turn could lead to autoantibody production against antigens that would not be exposed as frequently without chemotherapy. It is unknown whether the presence of autoantibodies in patients who develop rheumatic IRAEs varies based on prior exposure to chemotherapy. Our hypothesis in this pilot study is that patients with melanoma referred to rheumatology for rheumatic IRAEs from ICB who had prior chemotherapy would have a higher prevalence of autoantibodies compared to those who did not receive chemotherapy.

Methods: A total of 23 patients with melanoma who developed rheumatic IRAEs during treatment with ICB were seen at an academic medical center rheumatology clinic from September 1, 2017 to March 31, 2020. Demographic information, clinical characteristics/type of IRAEs, ICB treatments received including prior chemotherapy, and autoantibody profiles including ANA (indirect immunofluorescence using HEp-2 cell lines) were collected. An ANA titer of 1:40 was considered negative. Differences in ANA positivity between patients who did and did not receive chemotherapy were estimated by Fisher’s exact test.

Results: There were 23 patients with melanoma who had a rheumatic IRAE, mean age of 61 years, 52% female and 2 non-white patients, who received single agent ICB (65%) versus combination ICB. Of the 23 total patients, 11 (48%) had 1 or more autoantibodies: 5 (22%) ANAs, 3 (13%) RFs, 2 (9%) Ro/SSA antibodies, 1 (4%) ACPA and 1 (4%) dsDNA. ANA was present in 3/5 patients (60%) who received chemotherapy prior to ICB compared to 2/18 patients (11%) who did not (p=0.05). The most common rheumatic IRAE was inflammatory arthritis (70%) with 8/11 autoantibody positive, followed by myositis (13%) and PMR (9%).

Conclusion: About half of patients with melanoma who developed rheumatic IRAEs had one or more autoantibody. There was a higher prevalence of autoantibodies, specifically ANA, in patients who received chemotherapy prior to ICB. The majority of autoantibody positive patients developed inflammatory arthritis. Although this is a small pilot, the findings are consistent with the idea that prior chemotherapy, by exposing autoantigens, could influence the risk for autoantibody production and development of rheumatic IRAEs. Larger studies are needed to explore this idea and determine the importance of prior chemotherapy in risk stratification for rheumatic IRAEs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prevalence-of-autoantibodies-in-patients-with-melanoma-who-develop-rheumatic-immune-related-adverse-events-during-treatment-with-immune-checkpoint-blockade/