Preexisting immune-mediated inflammatory disease is associated with improved survival and increased toxicity in melanoma patients who receive immune checkpoint inhibitors.

Background: Immune-related adverse events (irAEs) are common, clinically significant autoinflammatory toxicities observed with immune checkpoint inhibitors (ICI). Preexisting immune-mediated inflammatory disease (pre-IMID) is considered a relative contraindication to ICI due to the risk of inciting flares. Improved understanding of the risks and benefits of treating pre-IMID patients with ICI is needed.

Methods: We studied melanoma patients treated with ICI and enrolled in a prospective clinicopathological database. We compiled a list of 23 immune-mediated inflammatory diseases and evaluated their presence prior to ICI. We tested the associations between pre-IMID and progression-free survival (PFS), overall survival (OS), and irAEs.

Results: In total, 483 melanoma patients were included in the study; 74 had pre-IMID and 409 did not. In patients receiving ICI as a standard of care (SoC), pre-IMID was significantly associated with irAEs (p = 0.04) as well as improved PFS (p = 0.024) and OS (p = 0.007). There was no significant association between pre-IMID and irAEs (p = 0.54), PFS (p = 0.197), or OS (p = 0.746) in patients treated through a clinical trial. Pre-IMID was significantly associated with improved OS in females (p = 0.012), but not in males (p = 0.35).

Conclusions: The dichotomy of the impact of pre-IMID on survival and irAEs in SoC versus clinical trial patients may reflect the inherit selection bias in patients accrued in clinical trials. Future mechanistic work is required to better understand the differences in outcomes between female and male pre-IMID patients. Our data challenge the notion that clinicians should avoid ICI in pre-IMID patients, although close monitoring and prospective clinical trials evaluating ICI in this population are warranted.