Autoantibody-positivity before and seroconversion during treatment with anti-PD-1 is associated with immune-related adverse events in patients with melanoma

医学 自身抗体 类风湿因子 内科学 抗甲状腺自身抗体 血清转化 不利影响 免疫学 黑色素瘤 抗体 甲状腺球蛋白 甲状腺 胃肠病学 癌症研究
作者
Jessica S.W. Borgers,Jessica S.W. Borgers,Jessica S.W. Borgers,Jessica S.W. Borgers,Jessica S.W. Borgers,Jessica S.W. Borgers,Jessica S.W. Borgers,Jessica S.W. Borgers,Jessica S.W. Borgers,Jessica S.W. Borgers,Jessica S.W. Borgers,Jessica S.W. Borgers,Jessica S.W. Borgers,Jessica S.W. Borgers
出处
期刊:Journal for ImmunoTherapy of Cancer [BMJ]
卷期号:12 (6): e009215-e009215
标识
DOI:10.1136/jitc-2024-009215
摘要

Introduction Treatment with the immune checkpoint inhibitor anti-programmed cell death protein-1 (PD-1) often causes immune-related adverse events (irAEs). Since irAEs resemble autoimmune diseases, autoantibodies might play a role and could potentially be used to identify patients at risk. Therefore, we investigated the association between autoantibody-positivity and toxicity as well as clinical response in patients with melanoma treated with anti-PD-1. Materials and methods This two-center, retrospective study included 143 patients with melanoma treated with anti-PD-1. Toxicities grade ≥2 and recurrences/responses were captured until 6 months after treatment initiation. Autoantibody measurements were performed at baseline and 3 months after treatment initiation, including IgM-rheumatoid factor (RF), antinuclear antibodies (ANA), extractable nuclear antigen, anti-cyclic citrullinated peptide antibodies (anti-CCP2) and anti-thyroid antibodies. Results 169 irAEs were experienced by 86/143 patients (137 grades 1–2, 32 grades 3–4), the most common being thyroiditis (n=25), dermatitis (n=24), and sicca problems (n=19). Patients with autoantibodies at baseline experienced more irAEs (p=0.001), predominantly associated with anti-thyroid antibodies and thyroid dysfunction. No association was observed between any irAE and anti-CCP2, RF or ANA. In women, baseline and on-treatment anti-thyroid antibody-positivity as well as seroconversion during treatment was associated with thyroid dysfunction. In men, this association was only observed on-treatment. The presence of autoantibodies was not associated with melanoma recurrence (p=0.776) or response (p=0.597). Conclusion The presence of autoantibodies prior to anti-PD-1 therapy is associated with irAEs in patients with melanoma. Both baseline positivity and seroconversion of anti-thyroid antibodies were strongly associated with thyroid dysfunction. This association was stronger in women, with all women who were baseline positive developing thyroid dysfunction.

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