POS0126 THE IMPACT OF PREEXISTING INFLAMMATORY ARTHRITIS ON SURVIVAL IN PATIENTS INITIATING IMMUNOTHERAPY WITH IMMUNE CHECKPOINT INHIBITORS FOR MALIGNANT MELANOMA: A NATIONWIDE PROSPECTIVE COHORT STUDY
Authors: H. Tenstad, C. Ruhlmann, S. Kjær, L. Bastholt, S. A. Just, S. Möller, H. M. Lindegaard
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Patients with inflammatory arthritis (IA) exhibit altered immune regulation due to disease mechanisms and long-term immunosuppressant treatment. Several malignant diseases have shown significant improvement with immune checkpoint inhibitors (ICI), amongst these are malignant melanoma (MM). ICIs enhance T-cell activation, prompting concerns about reduced efficacy in IA patients due to the disease's impact on immune regulation and immunosuppressant treatments. Moreover, individuals with preexisting autoimmune diseases face an increased risk of immune related adverse events (irAE) during ICI treatment, coupled with potential for exacerbation of their autoimmune condition. Studies suggest poorer cancer-related outcomes in IA patients, necessitating further investigation. <h3>Objectives:</h3> Evaluate the impact of IA and immunosuppressive treatments with disease-modifying antirheumatic drugs (DMARDs) on the efficacy of ICIs in patients with malignant melanoma. Primary outcomes: Differences in overall survival (OS) and progression-free survival (PFS) between patients with and without IA, and with or without DMARD treatment at ICI initiation. <h3>Methods:</h3> We established a nationwide, prospectively registered cohort utilizing high-quality data from the Danish Metastatic Melanoma Database (DAMMED) and Danish Rheumatologic Database (DANBIO) (Figure 1). Both DAMMED and DANBIO are comprehensive and validated Danish nationwide registries. DANBIO dates back to 2006 and DAMMED to 2013, providing high coverage real-world data on MM and IA respectively. We used DAMMED to identify individuals with MM treated with ICI between 2013 and 2022. Data was cross matched with DANBIO, identifying all individuals diagnosed with rheumatoid arthritis, psoriatic arthritis, and spondylarthritis diagnosed before ICI initiation. We further divided individuals with preexisting IA in subgroups based upon type of DMARD treatment within 3 months before ICI initiation (Figure 1). Conducting paired matched comparisons using Cox regression, outcomes (OS and PFS) were evaluated using Kaplan-Meier estimates between IA and non-IA patients and those with or without DMARD treatment at ICI initiation. Log rank testing were performed to test for significance. Matched comparisons considered gender, age, LDH level, melanoma type, ICI treatment regimen, melanoma stage, brain metastases and M1A disease. We matched 1 to 5 controls per case, depending on availability of controls. This comprehensive approach aims to provide insights into the impact of IA on immunotherapy efficacy in MM patients, utilizing robust nationwide databases. <h3>Results:</h3> We identified 91 patients with pre-existing IA, 41 patients were in treatment with methotrexate (MTX) at ICI initiation. Patients with pre-existing arthritis showed shorter PFS (hazard ratio (HR) =1.5, 95%CI 1.12-1.95, p=0.005) and OS (HR=1.4, 95%CI 1.00-1.9, p=0.05,), respectively (Figure 2). Median PFS in patients with IA was 4.2 months (95%CI 3.35-7.06) versus 10.2 months (95%CI 7.85-13.04) in the matched control group. Median OS in patients with IA was 22.86 months (95%CI 13.56-33.24) versus 34.00 months (26.22-43.10) in the matched control group. Patients treated with MTX showed a non-significant trend towards shorter PFS (p=0.17; 95% CI 0.88-2.01), with no observed difference in OS (Figure 2).We did not have enough data to analyze effect of other DMARDs than MTX. <h3>Conclusion:</h3> We show that MM patients undergoing ICI treatment with preexisting IA has shorter overall survival and progression-free survival, compared to non-IA patients. Although a trend towards shorter PFS was observed among patients treated with MTX, this difference was not statistically significant. Several factors could be involved in the shorter survival such as: Increased use of glucocorticoids, as well as abnormalities in immune regulationdue to IA and a known heightened risk of immune related adverse events (irAE) in patients with preexisting IA. Further research is imperative to understand the factors contributing to poorer outcomes in IA patient's undergoing ICI treatment. We intend to repeat the analysis with updated data in following years. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Helene Tenstad Astra-Zenica - paid for 30 minutes educational lecture on rheumatological manifestations due to immune checkpoint inhibitors, Christina Ruhlmann Christina H. Ruhlmann reports grants from Novo Nordisk Foundation and Helsinn Healthcare SA; personal fees from Bristol-Myers Squibb, Helsinn Healthcare SA, Merck Sharp &amp; Dohme, and Pharmanovia, outside the submitted work., Søren Kjær: None declared, Lars Bastholt: None declared, Søren Andreas Just: None declared, Sören Möller: None declared, Hanne Merete Lindegaard: None declared.