Background 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).
Objectives To evaluate the prevalence and type of rheumatic and musculoskeletal disorders in patients receiving ICI at a single institution (University Hospital of Bordeaux, France).
Methods 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.
Results 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.
Conclusions 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.
Disclosure of Interest None declared
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