Systemic lupus erythematosus patients eligible for chimeric antigen receptor T-cell therapy according to the 2024 EBMT and International Society for Cell and Gene Therapy expert-based recommendations: a 1-year clinical practice study in France

BACKGROUND AIMS: Systemic lupus erythematosus (SLE) is a rare and highly heterogeneous autoimmune disease in which standard treatment is based on corticosteroids and conventional or biological immunosuppressive drugs. In severe SLE patients (resistant to first- and second-line therapies), the 10-year mortality rate remains around 10-15%. Autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has recently demonstrated sustained remission in this subset of SLE patients, but the number of treated patients remains low. The objective of this study was to assess the clinical practices (CPs) and various challenges in recruiting severe SLE patients eligible for CAR T-cell therapy. METHODS: A 1-year (February 2024 to February 2025) retrospective multicenter study was conducted across seven certified autoimmune disease reference centers. All adult SLE patients fulfilling the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology criteria were screened for disease activity and severity according to the 2024 EBMT-International Society for Cell & Gene Therapy expert consensus. Eligibility for CAR T-cell or other non-cell and gene therapy trials and reasons for non-inclusion were analyzed. RESULTS: Among 1844 SLE patients screened over this 1-year retrospective study: 54 (2.9%) demonstrated severe disease criteria and, three (0.16 %) were ultimately treated by CAR- T while 49 were not selected for CAR T-cell trials because of either disease remission, lack of specific autoantibody, participation in other trials, physician/patient refusal or exclusion criteria at time of enrollment. CONCLUSIONS: Retrospective analysis of CPs showed that very few severe SLE patients were enrolled in the CAR T-cell trial despite eligibility criteria. Streamlined referral pathways, multidisciplinary coordination and improved physician education are needed to enhance access to advanced cell and gene therapies.