A propensity score–matched real-world analysis of immune checkpoint inhibitors in melanoma patients with autoimmune disease.

Abstract

9594 Background: Immune checkpoint inhibitors (ICIs) are foundational in the treatment of melanoma. However, patients with pre-existing autoimmune diseases (AD) have been excluded from pivotal ICI clinical trials and remain underrepresented in real-world outcome data. We conducted a propensity score–matched cohort study to evaluate the impact of pre-existing AD on clinical outcomes among melanoma patients treated with ICIs. Methods: A retrospective cohort study was performed using the TriNetX Research Network, including adult patients with melanoma treated with ICIs. ICI regimens included PD-1, PD-L1, and CTLA-4–based therapies. Patients with documented pre-existing AD were compared with patients without AD using 1:1 propensity score matching (PSM) for demographics, baseline corticosteroid use, laboratory values, and comorbidities. Outcomes included overall survival (OS) at 1 and 3 years; infections, corticosteroid exposure, and non-steroidal immunosuppressant exposure within 90 days of ICI initiation; and immune-related adverse events (irAEs), analyzed as a composite outcome and stratified by organ system (cardiac, pulmonary, endocrine, and dermatologic) within 180 days. Outcomes were assessed using hazard ratios (HRs), risk ratios (RRs), and 95% confidence intervals (CIs). Results: A total of 21,236 patients met inclusion criteria, including 3,372 with pre-existing AD and 17,863 without. After PSM, 3,372 patients were included in each cohort. Patients with AD demonstrated improved overall survival at both 1 and 3 years compared with those without AD (1-year HR 0.70, 95% CI 0.62-0.79; 3-year HR 0.76, 95% CI 0.70-0.84). Patients with AD were at increased risk for composite irAEs (RR 1.66, 95% CI 1.47–1.87). Organ-specific analyses demonstrated higher risks of cardiac (RR 3.29, 95% CI 2.02–5.34), endocrine (RR 1.48, 95% CI 1.22–1.81), and dermatologic irAEs (RR 1.46, 95% CI 1.22–1.73) among patients with AD. Patients with AD also had higher rates of corticosteroid (RR 1.23, 95% CI 1.18–1.28) and non-steroidal immunosuppressant exposure (RR 4.96, 95% CI 3.73–6.61), as well as increased risk of infection (RR 1.28, 95% CI 1.13–1.44). Conclusions: In this large real-world analysis, melanoma patients with pre-existing AD treated with ICIs demonstrated improved overall survival despite increased irAEs, immunosuppressant exposure, and infection. These findings challenge excluding patients with AD from receiving ICI therapy and support inclusion in future clinical trials. Outcome AD[n= 3,372] No-AD[n= 3,372] HR/RR [95% CI] 1-year OS 85.2% 79.8% 0.70 [0.62-0.79] 3-year OS 71.1% 65.2% 0.76 [0.70-0.84] Any irAE (180 days) 19.6% 11.8% 1.66 [1.47-1.87] Cardiac irAE 2.1% 0.6% 3.29 [2.02-5.34] Pulmonary irAE 0.8% 0.6% 1.34 [0.76-2.35] Endocrine irAE 7.0% 4.7% 1.48 [1.22-1.81] Dermatologic irAE 9.2% 6.3% 1.46 [1.22-1.73] Infection (90 days) 15.9% 12.6% 1.28 [1.13-1.44]