AB0032 CASE REPORT: ADVANCED MELANOMA PATIENT WITH FAVORABLE RESPONSE TO IMMUNE CHECKPOINT INHIBITOR TREATMENT SHOWS SEVERE ERYTHEMA CIRCINATUM WITH ANTI-SS-A ANTIBODIES

Background Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have been efficacious treatments in oncology. However, the use of ICI induces a large spectrum of immune side effects. The prevalence of autoimmune connective tissue diseases and the autoantibody profiles induced by ICI are largely unknown. The Ro52/TRIM21 antigen is known as a cytosolic Fc receptor that is found in almost all tissues. Its expression is regulated by interferons, and overexpression or hypoexpression has been observed in several cancers. Objectives In this study, we investigated autoantibodies produced after ICI treatments and analyzed the clinical characteristics of the patients. Methods Sera were collected from patients with unresectable metastatic or recurrent melanoma before and after treatment with ICIs such as ipilimumab, nivolumab or pembrolizumab. Autoantibodies were screened by Western blotting (WB) using A375 and HaCaT cell extracts. Antigenic proteins, which showed differences in reactivities in WB before versus after treatment, were purified by immunoprecipitation and analyzed by time-of-flight mass spectrometry. The identified proteins were tested for serum reactivities with ELISA. Results Of the 19 melanoma patients, 1 patient showed high titers of anti-SS-A/Ro52 and anti-SS-A/Ro60 antibodies after treatment. The other 18 melanoma patients were negative for both anti-SS-A/Ro52 and anti-SS-A/Ro60. Case presentation: An 81-year-old Japanese male patient with multiple metastatic melanomas on the face (Figure 1A) was judged as unresectable, and treatment with pembrolizumab was started. After the fifth pembrolizumab administration, a grade 2 skin rash appeared (Figure 1B). The multiple metastatic lesions and the primary melanoma showed significant reductions, without new cancer lesions (Figure 1C). Pembrolizumab was ceased after the ninth administration with grade 3 skin erythema, and systemic prednisolone (PSL) at 1mg/kg/day was started. No other subjective symptoms, such as sicca, fever or fatigue, were observed. A biopsy specimen of erythema circinatum on the back showed strong liquefaction degeneration, individual cell keratinization and exocytosis. The reactive 52kDa and 60kDa polypeptides in WB (Figure 1D) were presumed to be SS-A/Ro52 and SS-A/Ro60, respectively, and the serum was confirmed to be reactive with these antigens by ELISA. The skin symptoms and anti-SS-A/Ro52 and anti-SS-A/Ro60 antibodies remained after the PSL treatment. Some of the erythema left incomplete depigmentation of the skin (Figure 1E, F). Anti-SS-A/Ro52 and anti-SS-A/Ro60 antibody titers increased along with the skin symptom in this melanoma patient who was being treated with an ICI (Table 1). Conclusion Anti-SS-A/Ro52 and/or anti-SS-A/Ro60 may have some association with cancer immunity. References [1] Rhodes DA, Isenberg DA. TRIM21 and the Function of Antibodies inside Cells. Trends Immunol. 2017;38:916-926. [2] Nguyen JQ, Irby RB. TRIM21 is a novel regulator of Par-4 in colon and pancreatic cancer cells. Cancer Biol Ther. 2017;18:16-25. A. Primary melanoma lesion on the face. B. Systemic erythema circinatum. C. Primary melanoma lesion after the ninth pembrolizumab administration. D. Western blotting using A375 extract. E. Erythema circinatum. F. Remaining incomplete depigmentation. Disclosure of Interests None declared