Objective
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.
Methods
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.
Results
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.
Conclusion
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.
In elderly patients with advanced NSCLC, treatment allocation on the basis of CGA failed to improve the TFFS or OS but slightly reduced treatment toxicity.
Little is known about the natural history of precancerous bronchial lesions. Histological changes occurring in 416 bronchial intraepithelial lesions (104 high-risk subjects) were assessed over a 2-yr period, using repeated follow-up autofluorescence endoscopies. During the study, 6 of 36 normal epitheliums became dysplastic; 47 of 152 metaplasia evolved to low-grade dysplasia, two progressed to carcinoma in situ, and one to invasive cancer; 6 of 169 low-grade epithelial lesions progressed to a persistent severe dysplasia; 10 of 27 severe dysplastic lesions and 28 of 32 carcinoma in situ persisted or progressed, respectively (p = 0.0005, severe dysplasia versus carcinoma in situ 24 mo outcome). Carcinoma in situ appeared more frequent in patients with a prior history or concomitant cancer (p = 0.003). Persistence of smoking during the study did not influence high-grade lesion outcome. Progression of low-grade epithelial lesions during the study occurred only in patients with at least a high-grade lesion in another site at baseline (9 of 147 lesions, 6.1%). Our study suggests that low-grade epithelial lesions could be safely followed-up at 2 yr in patients without high-grade lesions at baseline, whereas severe dysplasia should be treated if they persist at 3 mo. Immediate treatment of carcinoma in situ appears warranted.
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