Background: Rheumatic immune-related adverse events (irAE) are associated with a better tumour response to immune checkpoint inhibitors (ICI). In contrast to other irAEs, their potentially chronic course may require long-term immunosuppressive treatment.

Objectives: Our registry-based study analyses real-world data on the characteristics and outcome of rheumatic irAEs and underlying malignancy. Herein, we present first evidence that these parameters and the optimal clinical management may differ depending on the tumour entity.

Methods: The TRheuMa registry is a prospective long-term observational study of a patient cohort suffering from rheumatic side effects of cancer therapies with focus on ICI. It is part of the MalheuR project initiated in July 2018 at the University Hospital Heidelberg to explore interrelations of malignancies and RMDs.

Results: 64 patients were recruited due to a rheumatic irAE under ICI treatment (nivolumab n=30, pembrolizumab n=33, ipilimumab n=12, PD-L1i n=5, ipi/nivo n=10) with a follow-up of up to 30 months. Of these, 47% had NSCLC and 41% melanoma. In local cohorts of patients receiving ICI, 4% of NSCLC (n total=888) and 13% of melanoma (n total=195) developed a rheumatic irAE. 7% of NSCLC and 23% of melanoma patients experienced a flare of a pre-existing RMD. De novo irAE mostly resembled phenotypes of spondyloarthritis both in NSCLC (43%) as well as in melanoma patients (33%). CRP levels were increased in 83% of NSCLC and 71% of melanoma patients. Almost all irAE patients showed autoantibody negativity and signs of inflammation in ultrasound examination (96%). Comparison of best responses to treatment in patients with and without rheumatic irAE in melanoma and without any irAE in NSCLC patients were as following: Complete remission (CR) in 48% vs. 4% of melanoma patients and partial remission (PR) in 68% vs. 41% of NSCLC patients. In accordance with our severity-based treatment algorithm, 25% of the melanoma patients in CR and 16% of the NSCLC patients in PR needed add-on DMARDs for sufficient irAE-treatment. ICI-treatment was discontinued in 7 cases (17% NSCLC, 8% melanoma)

Conclusion: Prospective real-world data from the TRheuMa-registry provide first evidence that rheumatic irAE have distinct characteristics depending on the underlying malignancy. Oncological outcome was better with rheumatic irAE than in their absence and this effect was more pronounced in melanoma patients despite a larger use of immunosuppressants for irAE-treatment.

Disclosure of Interests: Leonore Diekmann: None declared, Lea Daniello: None declared, Julia Kunz: None declared, Jan Leipe Consultant of: Pfizer; Novartis; Honoraria (self), Abbvie; Astra Zeneca; BMS; Celgene; Hospira; Janssen-Cilag; Gilead; LEO Pharma; Lilly; MSD; Roche; Sanofi; UCB., Grant/research support from: Research grant/Funding (self): Pfizer; Novartis; Honoraria (self), Hanns-Martin Lorenz Consultant of: Abbvie; BMS; MSD; Pfizer; Celgene; Roche; Chugai; Medac; GSK; Honoraria (self), Novartis; UCB; Janssen-Cilag; Astra Zeneca; Lilly, Grant/research support from: Research grant/Funding (institution): Abbvie; BMS; MSD; Pfizer; Celgene; Roche; Chugai; Medac; GSK; Honoraria (self), Research grant/Funding (institution), Novartis; UCB; Janssen-Cilag; Astra Zeneca; Lilly; Research grant/Funding (institution): Baxter; SOBI; Biogen; Actelion; Mundipharma; Bayer Vital; Octapharm; Sanofi; Hexal; Thermo Fischer; Shire., Jessica Hassel Consultant of: MDS; Honoraria (self): Roche; Novartis; Pierre Fabre., Grant/research support from: BMS; Honoraria (self), Karin Jordan Consultant of: Advisory/Consultancy: Amgen; Merck; MSD; Riemser; Helsinn; Tesaro; Kreussler; Voluntis; Pfizer; Pomme-med; Hexal., Petros Christopoulos Consultant of: advisory board/lecture fees from AstraZeneca, Boehringer Ingelheim, Chugai, Novartis, Pfizer, Roche, Takeda., Grant/research support from: research funding from AstraZeneca, Novartis, Roche, Takeda, Karolina Benesova Grant/research support from: Foundations and Awards” commission of the University of Heidelberg: University of Heidelberg; AbbVie; Novartis; Rheumaliga Baden-Württemberg e.V