Pos1567 outcomes and Predictors of Chronic Immune Checkpoint Inhibitor Induced Inflammatory Arthritis: Data From the Canadian Research Group of Rheumatology in Immuno-Oncology (Canrio) Retrospective Cohort

Abstract

BackgroundImmune checkpoint inhibitors (ICI) improve overall survival and progression-free survival in many types of malignancies and are the new pillar of cancer treatment[1]. ICIs harness a patient’s own immune system to fight their cancer. However, this activation of the immune system can result in off-target immune-related adverse events (irAEs). One of the most disabling irAE is inflammatory arthritis (ir-IA)[2]affecting up to 7.5% of those treated with ICI[3]. Unlike most irAE which usually resolve within a few months, ir-IA can become chronic and persist even after ICI cessation, requiring long term immunosuppression[4]. The factors associated with chronic ir-IA and its significance regarding tumor outcomes remain largely unknown. With the increasing use of ICI in the adjuvant therapy, it is important to understand predictors and outcomes of chronic ir-IA in order to best counsel patients.ObjectivesTo determine predictors and outcomes of chronic ir-IA in cancer patients exposed to ICI.MethodsThe CanRIO group, established since 2018, includes 9 academic sites in Canada and aims to describe the clinical presentation, management and outcomes of patients who developed rheumatic irAE (Rh-irAE) or those with pre-existing autoimmune diseases exposed to ICI using standardized data collection. The sites pooled data to develop a retrospective cohort of patients identified as having a Rh-irAE. We identified patients who developed ir-IA defined by new onset joint tenderness or synovitis in the absence of pre-existing rheumatic disease and who had at least 3 months of follow-up following ICI cessation. Chronic ir-IA was defined as having either persistent symptoms of ir-IA or the continued use of prednisone or DMARDs 3 months after ICI cessation.ResultsThe CanRIO Retrospective Cohort included 193 ir-IA individuals of which 54 met our inclusion criteria. Forty-five of 54 (83%) had chronic ir-IA. Fifteen (33%) were female. Nineteen (42%) patients with chronic ir-IA had melanoma, 14 (31%) lung cancer and 8 (18%) genito-urinary cancer. Thirty-three (73%) were treated with anti PD-1/PD-L1, 14 (31%) with combination and none with anti-CTLA-4 only. Thirty-five (78%) were treated with conventional DMARDs and 1 (2%) with biologic DMARDs. Univariable logistic regression showed that ir-IA was more likely to become chronic in those with peripheral synovitis compared with those who did not have peripheral synovitis at presentation, (Table 1). Patients with chronic ir-IA had greater overall survival and progression-free survival compared to those with acute ir-IA (log rank tests, p<0.01), (Figure 1).ConclusionA large proportion of ir-IA becomes chronic. The presence of synovitis at presentation is associated with arthritis persistence. Ir-IA is associated with improved overall survival and progression-free survival.References[1]Sharma, P., et al., Cancer Discov, 2021.[2]Roberts, J., et al., Autoimmun Rev, 2020.[3]Suarez-Almazor, M.E., et al., Support Care Cancer, 2020.[4]Braaten, T.J., et al., Ann Rheum Dis, 2020.Table 1.Logistic regression model: univariable analysis to assess factors associated with chronic ir-IA compared with acute ir-IAChronic ir-IACharacteristicOR95% CIp valueMale1.000.22-4.561.00Age0.980.93-1.040.54Past or current smoking history0.610.11-3.380.58Family history of rheumatic autoimmune disease1.830.20-16.770.59One or more other irAE2.330.43-12.530.323Combination ICI1.570.29-8.610.29Duration of ICI therapy1.040.98-1.150.95Polyarthritis1.550.32-7.510.31Peripheral synovitis121.95-73.970.007CDAI1.070.95-1.200.95C-reactive protein1.020.99-1.050.17Time from ir-IA onsets to treatment0.990.85-1.150.89irAE: immune-related adverse event; ICI: immune checkpoint inhibitors; CDAI: clinical disease activity indexFigure 1.Kaplan-Meier curves for overall survival and progression-free survival based on acute and chronic ir-IAAcknowledgements:NIL.Disclosure of InterestsAlexandra Ladouceur: None declared, Lourdes Gonzalez Arreola: None declared, Shahin Jamal: None declared, Marie Hudson Consultant of: Boehringer Ingelheim.Grant/research support from: Bristol-Myers Squibb, Boehringer Ingelheim; Clinical studies: Astra-Zeneca, Janet Pope: None declared, Sabrina Hoa: None declared, Janet Roberts: None declared, David Moon: None declared, Ammana Karmali: None declared, Tatiana Nevskaya: None declared, Emma Schmidt: None declared, Nader Toban: None declared, Lindsay Cho: None declared, Thomas Barnetche: None declared, Carrie Ye: None declared.