Safety and Efficacy of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Disease: A Nationwide, Multicenter Cohort Study

TLDR

Immune checkpoint inhibitors frequently trigger immune‑related adverse events, leading to the exclusion of most patients with preexisting autoimmune diseases from clinical trials, where the most common conditions are psoriasis, rheumatoid arthritis, and inflammatory bowel disease. This study aimed to evaluate the safety and efficacy of ICIs in cancer patients with preexisting autoimmune disease. A retrospective cohort of 112 adults from three French national networks was followed for a median of 8 months to assess autoimmune flares, other IRAEs, and cancer response, with 22 % on immunosuppressive therapy at ICI initiation. Among 112 patients, 71 % experienced an autoimmune flare or other IRAE, 21 % required ICI discontinuation, and baseline immunosuppressive therapy was linked to shorter progression‑free survival (3.8 vs 12 months) and poorer outcomes, though most events were manageable without stopping treatment.

Abstract

Immune checkpoint inhibitors (ICIs) for cancer therapy frequently induce immune-related adverse effects (IRAEs). Therefore, most patients with preexisting autoimmune diseases have been excluded from clinical trials of ICIs. This study was undertaken to evaluate the safety and efficacy of ICIs in patients with preexisting autoimmune disease and cancer.A retrospective cohort study was conducted from January 2017 to January 2018 via 3 French national networks of experts in oncology and autoimmunity. Adults with preexisting autoimmune disease who were receiving ICIs were assessed for the occurrence of flare of preexisting autoimmune disease, other IRAEs, and cancer response.The study included 112 patients who were followed up for a median of 8 months. The most frequent preexisting autoimmune diseases were psoriasis (n = 31), rheumatoid arthritis (n = 20), and inflammatory bowel disease (n = 14). Twenty-four patients (22%) were receiving immunosuppressive therapy at ICI initiation. Autoimmune disease flare and/or other IRAE(s) occurred in 79 patients (71%), including flare of preexisting autoimmune disease in 53 patients (47%) and/or other IRAE(s) in 47 patients (42%), with a need for immunosuppressive therapy in 48 patients (43%) and permanent discontinuation of ICI in 24 patients (21%). The median progression-free survival was shorter in patients receiving immunosuppressive therapy at ICI initiation (3.8 months versus 12 months; P = 0.006), confirmed by multivariable analysis. The median progression-free survival was shorter in patients who experienced a flare of preexisting autoimmune disease or other IRAE, with a trend toward better survival in the subgroup without immunosuppressant use or ICI discontinuation.Our findings indicate that flares or IRAEs occur frequently but are mostly manageable without ICI discontinuation in patients with a preexisting autoimmune disease. Immunosuppressive therapy at baseline is associated with poorer outcomes.