Safety and Efficacy of Immune Checkpoint Inhibitors in Cancer Patients and Preexisting Autoimmune Disease: A Systematic Review and Meta-Analysis in Non–Small-Cell Lung Cancer

Abstract

Cancer patients with preexisting autoimmune diseases (AID) have been traditionally excluded from clinical trials of immune checkpoint inhibitors (ICI) due to concerns for toxicity. As indications for ICI expand, more data are needed on the safety and efficacy of ICI treatment in cancer patients with AID. We systematically searched for studies consisting of NSCLC, AID, ICI, treatment response, and adverse events. Outcomes of interest include incidence of autoimmune flare, irAE, response rate, and ICI discontinuation. Study data were pooled using random-effects meta-analysis. Data were extracted from 24 cohort studies, consisting of 11,567 cancer patients (3774 NSCLC patients and 1157 with AID). Pooled analysis revealed an AID flare incidence of 36% (95% CI, 27%-46%) in all cancers and 23% (95% CI, 9%-40%) in NSCLC. Preexisting AID was associated with an increased risk of de novo irAE in all cancer patients (RR 1.38, 95% CI, 1.16-1.65) and NSCLC patients (RR 1.51, 95% CI, 1.12-2.03). There was no difference in de novo grade 3 to 4 irAE and tumor response between cancer patients with and without AID. However, in NSCLC patients, preexisting AID was associated with a 2-fold increased risk of de novo grade 3 to 4 irAE (RR 1.95, 95% CI, 1.01-3.75) but also better tumor response in achieving a complete or partial response (RR 1.56, 95% CI, 1.19-2.04). NSCLC patients with AID are at a higher risk of grade 3 to 4 irAE but are more likely to achieve treatment response. Prospective studies focused on optimizing immunotherapeutic strategies are needed to improve outcomes for NSCLC patients with AID.