FRI0584 Rheumatic and musculoskeletal disorders related to immune checkpoint inhibitors in cancer patients: a prospective single-institution study
Authors: K Marie, L Rouxel, R Veillon, F Martin, C Dutriaux, A Pham-Ledard, S Prey, M Beylot-Barry, M Gross-Goupil, B Bannwarth, C Richez, N Mehsen-Cetre, T Schaeverbeke
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) axis have been a major advance in cancer immunotherapy. By enhancing T cell activity, unprecedented long-lasting tumour responses are observed in selected cancers but some patients experience immune related adverse events (irAE). <h3>Objectives</h3> To evaluate the prevalence and type of rheumatic and musculoskeletal disorders in patients receiving ICI at a single institution (University Hospital of Bordeaux, France). <h3>Methods</h3> All cancer patients with musculoskeletal disorders while receiving ICI were referred to our rheumatology department. For each referred patient, an experienced rheumatologist performed a comprehensive clinical evaluation. Blood tests (inflammatory markers, serum creatine kinase, autoantibodies) and imaging (X-rays, ultrasound) were obtained according to clinical findings. HLA-DR phenotyping was also performed for some patients to search for shared epitope. <h3>Results</h3> From September 2015 to December 2016, 329 patients received ICI (anti CTLA-4: n=38; anti PD-1: n=251; anti PD-L1: n=29; combination anti CTLA-4/anti PD-1: n=11) and 21 patients were referred to our rheumatology department (6.4%). Mean age was 65 years and cancer types included melanoma (n=10), non small cell lung cancer (n=9), Merkel carcinoma (n=1) and renal carcinoma (n=1). All musculoskeletal disorders occurred in patients receiving anti PD-1 (nivolumab: n=12; pembrolizumab: n=6) or anti PD-L1 (avelumab: n=2; atezolizumab: n=1), with a median exposure time of 90 days (range: 1–650 days). There were two distinct clinical presentations: 1) inflammatory arthritis (IA) mimicking either rheumatoid arthritis (n=5) or polymyalgia rheumatica (n=8) and, 2) non-inflammatory musculoskeletal conditions (n=8). Of note, one patient was anti-CCP positive but negative for RF. Shared epitope HLA-DRB1 *01:01 was present in 4 patients. Eleven patients required corticosteroid therapy with a median dose of 15mg/day (range: 7–30 mg/day). Non-inflammatory disorders were easily managed with NSAIDs, analgesics and/or physiotherapy. ICI treatment was temporarily discontinued in one patient only, in line with the clinical trial protocol. To date, there was a partial or complete tumour response to ICI in 10 patients whereas 3 had stable disease and 7 had progressive disease. Tumour response or stable disease was observed in 11 of 12 patients with IA but only in 2 of 8 patients with non-inflammatory conditions. <h3>Conclusions</h3> In our series, patients with immune-related IA mimicking rheumatoid arthritis and polymyalgia rheumatica were responsive to low-to-moderate dose of prednisone and did not require ICI discontinuation. Furthermore, tumour response was frequently observed in such patients. <h3>Disclosure of Interest</h3> None declared