POS0124 SYSTEMIC LUPUS RISK ASSESSMENT IN CANCER IMMUNOTHERAPY: A COMPREHENSIVE STUDY COMPARING NIVOLUMAB AND IPILIMUMAB COMBINATION TO PEMBROLIZUMAB - INSIGHTS FROM A RETROSPECTIVE COHORT ANALYSIS
Authors: I. Tskhakaia, I. Tan, I. Lemonjava, N. Gudushauri
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Immunotherapy has revolutionized cancer treatment, with immune checkpoint inhibitors like Nivolumab and Ipilimumab in combination and Pembrolizumab showcasing remarkable efficacy across various malignancies. While these therapies offer promising outcomes, the emergence of autoimmune adverse events has prompted concerns. Specifically, systemic lupus erythematosus (SLE) is among the observed complications. Understanding the differential risks associated with Nivolumab and Ipilimumab versus Pembrolizumab is crucial. This study delves into a comprehensive analysis of clinical data, emphasizing the need for insights to inform clinicians about the distinct immunological impacts, guiding optimal cancer treatment strategies, and shaping the future landscape of cancer immunotherapy. <h3>Objectives:</h3> In a retrospective, longitudinal, matched cohort study, we explored the correlation between systemic lupus erythematosus (SLE) risk in patients treated with a combination of nivolumab and ipilimumab versus pembrolizumab. Leveraging the TrinetX database comprising electronic health records from 79 global healthcare organizations, our investigation provides valuable insights into the comparative autoimmune risks associated with these immunotherapies. <h3>Methods:</h3> In this study, patients aged 18-99 were assigned to either the nivolumab and ipilimumab group or the pembrolizumab group. Inclusion criteria were standardized across both groups, encompassing various cancer types such as lung, renal cell carcinoma, colon, head and neck, cervical, skin melanoma, esophageal, biliary, breast, endometrial, Hodgkin lymphoma, stomach, or non-melanoma skin cancer. Exclusion criteria involved using alternative PD-1, PD-L1, CTLA-4, and LAG-3 agents, with strict mutual exclusion between nivolumab-ipilimumab and pembrolizumab groups. To ensure cohort comparability, we did a 1:1 propensity score matching analysis adjusting for age, gender, ethnicity, medication use (musculoskeletal, antineoplastic, immunologic, hormone/synthetic, dermatological, and gastrointestinal), as well as diagnoses and numeric laboratory values. The index event comprised the appearance of oncological diagnosis and checkpoint inhibitors in patient records. The primary outcome was the diagnosis of systemic lupus erythematosus (SLE), which was meticulously monitored, excluding patients with pre-existing SLE (Table 1). <h3>Results:</h3> 7,159 patients in the Nivolumab and Ipilimumab group and 43,606 patients in the Pembrolizumab group entered the analysis, compared to Pembrolizumab group, the combination group was significantly younger (65.4 +-12.9 vs. 67.8 +-13.5; p&lt;0.0001) and had less females (33.5% vs. 49.2%; p&lt;0.0001). Our initial unmatched analysis disclosed a 0.5% risk of systemic lupus erythematosus in the combination therapy group compared to 0.15% in the Pembrolizumab group. This yielded a risk ratio of 3.13 (95% CI: 2.084, 4.703, p-value &lt;0.0001). Post-propensity score matching, with 7,156 patients in each group, the outcome maintained statistical significance, revealing a risk ratio of 2.93 (95% CI: 1.52, 5.63, p-value 0.0007) (Table 2). Discrepancies between the total number of patients before and after analysis mean that patients were excluded due to the presence of outcomes prior to the index period. <h3>Conclusion:</h3> Our study demonstrated a potentially elevated risk of systemic lupus erythematosus (SLE) associated with the combination of nivolumab and ipilimumab compared to pembrolizumab in cancer patients. This emphasizes the need for monitoring autoimmune adverse events during immunotherapy. While our results contribute valuable insights, prospective studies are imperative to further elucidate and validate these associations and provide a more comprehensive understanding of the risks associated with these immunotherapeutic regimens. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>