Abstract
e21586 Background: Immune checkpoint inhibition (ICI) improves progression-free (PFS) and overall survival (OS) for patients with metastatic melanoma (MM), but induces immune-related adverse events (irAEs). Pre-existing autoimmune disease (pre-AI) is considered a relative contraindication due to concerns of inciting autoimmune flare. We here tested the impact of pre-AI on both the survival and irAEs in MM patients treated with ICI. Methods: We examined MM patients treated with ICI who were enrolled in a clinicopathological database at NYULH with protocol-driven prospective follow up. We compiled a comprehensive list of 23 autoimmune diseases and examined the presence of these diseases prior to ICI treatment. We tested the associations between pre-AI and PFS, OS, and irAEs both in univariate and multivariate models. Results: 74/485 (15.3%) patients, who received 718 lines of ICI treatment as either standard of care or in clinical trials, had pre-AI, most commonly asthma (n=42), inflammatory bowel disease (n=9), psoriasis (n=9), rheumatoid arthritis (n=7), and eczema (n=6). In patients receiving ICI as standard of care (n=535), pre-AI was associated with irAEs (P=0.05) as well as with significantly improved PFS (P=0.024) and OS (P=0.007), controlling for patients’ sex, age, stage, ECOG status, and treatment line (1st line versus 2nd or 3rd line). However, no associations were observed between pre-AI and PFS (P=0.2) or irAEs (P=0.54) in the clinical trial group. Conclusions: Our data demonstrate the disparate impact of pre-AI on response and irAEs in standard of care versus the highly controlled clinical trial settings, and underscore the importance of examining the complex interaction between autoimmune disease before and after initiation of ICI. Our data also challenge the notion that clinicians should avoid use of ICI in pre-AI patients. More mechanistic research is needed to understand how to uncouple ICI response from toxicity.
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