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BackgroundImmune Checkpoint Inhibitors (ICI) have altered the landscape of cancer therapy. However, toxicities are common and up to 80% of patients will develop immune-related adverse events (irAE), including rheumatic irAEs (Rh-irAE), which can often limit their cancer treatment. Our knowledge of clinical manifestations and optimal management of patients with Rh-irAE continues to evolve as these agents are being used to treat a wider variety of cancers. Currently available data is limited to retrospective case series and case reports. There is also scarce data on the use of ICI in patients with pre-existing autoimmune disease (PAD) as these patients are often excluded from clinical trials.ObjectivesTo describe the clinical presentation, management and early outcomes of patients exposed to ICI with Rh-irAE or PAD recruited and followed prospectively from multiple sites across Canada.MethodsAdult patients with Rh-irAE from cancer immunotherapy (CTLA-4, PD-1 or PDL-1 inhibitors) or those with PAD exposed to cancer immunotherapy are prospectively recruited across 9 academic sites in Canada. Standardized clinical and biologic data are also collected. We describe clinical characteristics and management of patients recruited between January 2020 and October 2021, stratified based on the presence or absence of PAD.Results103 patients were recruited from 9 sites. From those, 85 had Rh-irAE, 47 had pre-existing musculoskeletal and rheumatic diseases, and 20 had other PAD. The most frequent Rh-irAE were joint manifestations (n = 73). Other Rh-irAE included muscle symptoms (n = 7), connective tissue disease (n = 6), vasculitis (n=2) and sarcoid (n = 3). Prednisone was the most common treatment (n = 53). Intraarticular corticosteroids were used in 7 patients. Eleven patients required conventional synthetic disease-modifying anti-rheumatic drugs (DMARD) and only one required biologic DMARD to control the Rh-irAE. Anti-PD-1 therapies were the most used ICI (56.3%), followed by combination therapy (35.9%). Response to index immunotherapy at 6 months was available for 21 patients. Most patients had partial response (57.1%) and only 4 patients had tumor progression (19.1%). The ICI was permanently discontinued due to an irAE in 21 patients (38.1% with PAD and 61.9% without PAD). There were no deaths related to Rh-irAE.ConclusionThe initial sample of the CanRIO prospective national cohort suggests that demographic characteristics and tumor representation in people with PAD and without PAD is similar. Patients with PAD are less likely to receive combination therapy (n= 12 vs. n=25) and are less likely to have tumor progression on ICI (n=1) compared to those without PAD (n=3). Selection bias is noted in this initial sample since half of recruited patients have PAD. The CanRIO cohort provides valuable insight into real-world spectrum and management of Rh-irAE secondary to immunotherapy for cancer.Disclosure of InterestsShahin Jamal Grant/research support from: CanRIO has received financial support from BMS and Organon, Lourdes Gonzalez Arreola: None declared, Julia Tan: None declared, Carrie Ye: None declared, Janet Roberts: None declared, Aurore Fifi-Mah: None declared, Marie Hudson: None declared, Sabrina Hoa: None declared, Janet Pope: None declared, Ines Colmegna: None declared, C. Thomas Appleton: None declared

BackgroundImmune checkpoint inhibitors (ICI) have changed the landscape of treatment for many cancers. However, most cancer clinical trials for ICI excluded patients with pre-existing autoimmune disease (PAD). Efficacy and safety data on the use of ICI in patients with rheumatic PAD (Rh-PAD) is limited to retrospective case series and reports, and many do not differentiate between Rh-PAD and non-rheumatic PAD. In addition, little is known about optimal use of concurrent immunosuppression and its impact on PAD flares and development of de novo irAE. There is some data that patients on immunosuppression at baseline are at risk for poorer tumor outcomes [1].ObjectivesTo explore the safety and efficacy of ICI in patients with Rh-PAD and to determine if immunosuppression at baseline impacts risk of PAD flare, de-novo irAE and early tumor outcomes using data from the CanRIO prospective cohort.MethodsThe CanRIO cohort includes adult patients with Rh-PAD treated with immune checkpoint inhibitors (ICI, including CTLA-4, PD-1 or PDL-1 inhibitors), recruited across 9 Canadian academic sites and followed prospectively at regular intervals as per a standardized study protocol. In this study, we evaluated patients with Rh-PAD who received at least one dose of ICI.ResultsForty patients with Rh-PADs were recruited into the CanRIO prospective cohort between Jan 2020 and Nov 2022, including 14 (35%) with rheumatoid arthritis, 11 (27.5%) psoriatic arthritis, 7 (17.5%) polymyalgia rheumatica, 5 (12.5%) ankylosing spondylitis and 7 (17.5%) other. The most frequently observed cancers were melanoma 14 (35%) and lung cancer 10 (25%), with stage 3 and stage 4 disease each making up 37.5% of all cases. 25 patients (62.5%) were on baseline immunosuppression prior to ICI start. Anti-PD-1 therapy was most common (45%), followed by combination ICI therapy (22.5%), with a median exposure of 2 months (IQR: 0.5-3.0). Over a median (IQR) follow-up of 3.0 (1.0–6.0) months, 55% experienced a de-novo irAE (68.2% with rh-irAE; of which 46.7% were on baseline immunosuppression), 25% had Rh-PAD flare, of which 60% were on baseline immunosuppression. Of these, 40% were severe (of which 50% on baseline immunosuppression); 70% required corticosteroid treatment; and 40% required a change in immunosuppression. ICI was continued in 50%, transiently held or delayed in 40% and stopped in only 10%. Of the 9 patients on baseline immunosuppression who had been re-staged, 8 had a favorable tumor response (i.e., stabilization, partial or complete response) and only 1 had disease progression.ConclusionEarly data from patients with Rh-PAD in the CanRIO multi-center prospective cohort suggests that (1) ICI can be effective for cancer treatment in patients with Rh-PAD and should be offered as indicated; (2) flares of Rh-PAD are common but can be managed with corticosteroids or escalation of immunosuppression; (3) baseline immunosuppression did not significantly change rate of de-novo irAE or rate/severity of PAD flare (3) most patients with Rh-PADs had good tumour response despite baseline immunosuppression.Reference[1]Tison A, Quéré G, Misery L, Funck-Brentano E, Danlos FX, Routier E, et al. Safety and efficacy of immune checkpoint inhibitors in patients with cancer and preexisting autoimmune disease: A nationwide, Multicenter Cohort Study. Arthritis & Rheumatology. 2019;71(12):2100–11.AcknowledgementsWe would like to thank Bristol-Myers Squibb, Merck, and CIORA (Canadian Initiative for Outcomes in Rheumatology cAre) for supporting this study. This content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsors listed here. This research was conducted as part of the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO).Disclosure of InterestsLourdes Gonzalez Arreola: None declared, Jeremiah Tan: None declared, Alexandra Ladouceur: None declared, Marie Hudson Consultant of: Consulting fees: Boehringer Ingelheim, Grant/research support from: Unrestricted research grants: Bristol-Myers Squibb, Boehringer Ingelheim; Clinical studies: Astra-Zeneca, Carrie Ye: None declared, Janet Roberts: None declared, Aurore Fifi-Mah: None declared, May Choi: None declared, Sabrina Hoa: None declared, C. Thomas Appleton: None declared, Janet Pope: None declared, Nancy Maltez: None declared, Shahin Jamal: None declared.

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.