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

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.

Validation of the French version of the London Chest Activity of Daily Living scale and the Dyspnea-12 questionnaire.

Introduction: Eighty percent of COPD patients experience dyspnea during activities of daily life (ADL). To the best of our knowledge, the Modified Medical Research Council (MMRC) dyspnea scale is the only validated scale designed to quantify dyspnea during ADL available in the French language. Two other instruments are only available in English versions: the London Chest Activity of Daily Living (LCADL) scale that allows a specific evaluation of dyspnea during ADL and the Dyspnea-12 questionnaire that evaluates the affective (emotional) and sensory components of dyspnea in daily life. The aim of this study was to translate and validate French versions of both LCADL and Dyspnea-12 questionnaires and to determine the reliability of these versions for the evaluation of dyspnea in severe to very severe COPD patients. Methods: Both translation and cultural adaptation were based on Beaton's recommendations. Fifty consecutive patients completed the French version of LCADL and Dyspnea-12 and other questionnaires (MMRC, Saint George's Respiratory Questionnaire [SGRQ], Hospital Anxiety and Depression [HAD]), at a 2-week interval. Internal consistency, validity, and reliability of LCADL and Dyspnea-12 were evaluated. Results: The French version of LCADL and Dyspnea-12 demonstrated good internal consistency with Cronbach's α of, respectively, 0.84 and 0.91. LCADL was correlated significantly with item activity of SGRQ (ρ=0.55, p<0.001), total score of SGRQ (ρ=0.63, p<0.001), item impact of SGRQ (ρ=0.57, p<0.001), and HAD-depression (HAD-D) (ρ=0.47, p=0.001); and Dyspnea-12 was correlated significantly with MMRC (ρ=0.39, p<0.001), HAD-anxiety (ρ=0.64, p<0.001), and HAD-D (ρ=0.64, p<0.001). The French version of LCADL and Dyspnea-12 demonstrated good test-retest reliability with, respectively, intraclass coefficient =0.84 (p<0.001) and 0.91 (p<0.001). Conclusion: The French versions of LCADL and Dyspnea-12 questionnaires are promising tools to evaluate dyspnea in severe to very severe COPD patients.