1809O - TRheuMa registry provides real world data on rheumatic immune-related adverse events

Background

Rheumatic immune-related adverse events (irAEs) are associated with better tumour response to immune checkpoint inhibitors (ICI). Research on this immunological intersection between malignancies and rheumatic and musculoskeletal diseases (RMDs) offers the opportunity for better patient centred care and scientific progress. A registry-based study is an ideal approach to obtain real world data on characteristics and optimal clinical management of rheumatic irAEs.

Methods

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

Results

So far, 57 patients were recruited due to a rheumatic irAE under ICI treatment (nivolumab n=29, pembrolizumab n=26, ipilimumab n=11, PD-L1i n=4, combined ICI n=10). Of these, 45.6% had NSCLC and 40.4% melanoma. 15.8% experienced a flare of a pre-existing RMD, 7.0% an initial manifestation of a classical RMD. De novo irAEs mostly resembled phenotypes of rheumatoid arthritis (15.8%), polymyalgia rheumatica (14.0%) and spondyloarthritis (38.6%), but differed in laboratory findings with elevated CRP-levels in 73.7% (28.1% >50mg/l) and mostly autoantibody negativity. The majority (77.2%) showed signs of inflammation in ultrasound examination with mostly symmetrical (65.9%) synovialitis (72.7%) and/or tenosynovialitis (68.2%). We developed a severity-based treatment algorithm: in 54.4%, ≤10mg prednisone +/- NSAID were sufficient, 12.3% required add-on cs-/bDMARD. ICI-treatment was discontinued in 5 cases (8.8%). Complete remission of melanoma was observed in 39% of patients with irAE vs. 4% in a historical control without irAE. Additional irAEs were observed in 52.2% of melanoma and 15.4% of NSCLC patients.

Conclusions

Prospective real world data from the TRheuMa-registry show that rheumatic irAEs mostly resemble classical RMDs with some distinct characteristics. Our clinical management strategy was effective and underlines our patient centred approach. Future research agenda includes long-term observation of irAE and specifically oncological outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Karolina Benesova.

Funding

Has not received any funding.

Disclosure

K. Benesova: Research grant/Funding (self), \"Foundations and Awards” commission of the University of Heidelberg: University of Heidelberg; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AbbVie; Gilead; Novartis; Honoraria (self): Medac; MSD; Roche; Travel/Accommodation/Expenses: Mundipharma; Research grant/Funding (institution): Rheumaliga Baden-Württemberg e.V.; Honoraria (self), Travel/Accommodation/Expenses: Janssen; BMS; Pfizer; UCB. H-M. Lorenz:Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Abbvie; BMS; MSD; Pfizer; Celgene; Roche; Chugai; Medac; GSK; Honoraria (self), Advisory/Consultancy, 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. J. Leipe: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer; Novartis; Honoraria (self), Advisory/Consultancy: Abbvie; Astra Zeneca; BMS; Celgene; Hospira; Janssen-Cilag; Gilead; LEO Pharma; Lilly; MSD; Roche; Sanofi; UCB. J.C. Hassel: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy: MDS; Honoraria (self): Roche; Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre. K. Jordan: Honoraria (self), Advisory/Consultancy: Amgen; Merck; MSD; Riemser; Helsinn; Tesaro; Kreussler; Voluntis; Pfizer; Pomme-med; Hexal. All other authors have declared no conflicts of interest.