Immunotherapy in patients with autoimmune disease

Immune checkpoint inhibitors (ICIs) such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) inhibitors are widely used for the treatment of multiple cancers. Seven of these agents are currently FDA approved in the US as first or second line options for solid tumors and hematologic malignancies. These agents work by downregulating pathways that suppress T-cell activation and thereby mounting an immune response to the tumor. In general, ICI are well tolerated with only mild to moderate toxicity. However, in some patients severe immune-related adverse events (irAEs) that mimic the presentation of autoimmune diseases (AID) may occur. It is believed that irAEs occur due to disruption of immunologic self-tolerance, a mechanism that also seems to explain AID. Patients with pre-existing AID are usually excluded from prospective clinical trials due to concerns for flares of the underline AID. There is limited retrospective evidence supporting the use of ICI in patients with some pre-existing AID. These patients have an increased risk of malignancy and there is an unmet need to study ICIs in this population. This manuscript intends to review the current available evidence for the safety and activity of ICIs in patients with pre-existing AID. We summarize the reported use of ICI in patients with pre-existing AID according to the primary tumor site and type of ICI used.