Pre-existing Autoimmune Diseases and Immune Checkpoint Inhibitors for Cancer Treatment: Considerations About Initiation, Flares, Immune-Related Adverse Events, and Cancer Progression

Abstract

Immune checkpoint inhibitors (ICI) are increasingly used to treat a variety of cancer types. Patients with pre-existing autoimmune diseases may be vulnerable to underlying disease flare as well as immune-related adverse events (irAE). There has been concern that immunosuppression needed to control the autoimmune disease may blunt ICI efficacy. Much of the literature is focused on diverse pre-existing autoimmune diseases, which may limit conclusions to specific diseases. There is a growing literature of specific diseases, such as pre-existing rheumatoid arthritis, with outcomes after ICI. Overall, nearly half of patients with pre-existing autoimmune disease flare after ICI but these vary in timing and severity. Data on management of pre-existing autoimmune disease flares are mostly based on case reports and case series, but typical therapies can often be used successfully. While patients with pre-existing autoimmune diseases can experience irAE in other organ systems, these are similar in frequency or may even be lower than non-autoimmune comparators due to the immune system being primed for autoimmune disease flare. There is no consistent association of pre-existing autoimmune disease with worsened mortality. Epidemiologic study design issues such as immortal time bias and competing risk of mortality need to be accounted for when studying post-baseline outcomes such as autoimmune disease flare or irAE risk. While more work is needed to investigate cancer safety of immunosuppression, the current data suggest that patients with pre-existing autoimmune disease can safely receive ICI to treat cancer.