Efficacy and safety of CD19 CAR T-cell therapy in autoimmune disease
Müller F, Taubmann J, Bucci L, et al. CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series With Follow-Up. New England Journal of Medicine. 2024; (doi: 10.1056/NEJMoa2308917).
Chimeric antigen receptor (CAR) T-cell therapy could have a future role in managing autoimmune disorders, based on emerging evidence. Researchers suspected ablation of B cells might "reset" rogue autoimmunity in these diseases, potentially laying the foundation for durable drug-free remission. They investigated the theory in a case series involving eight patients with severe systemic lupus erythematosus (SLE), three with idiopathic inflammatory myositis, and four with systemic sclerosis. After fludarabine/cyclophosphamide preconditioning, each received a single infusion of CD19 CAR T cells. At a median 15-month follow-up, all SLE patients achieved remission per the Definition of Remission in SLE (DORIS) criteria; all patients with idiopathic inflammatory myositis produced a major clinical response as defined by the American College of Rheumatoloy-European League against Rheumatism (ACR-EULAR) metric, and all patients with systemic sclerosis reduced their score on the European Scleroderma Trials and Research Group (EUSTAR) activity index. Adverse events were minimal, with no evidence of high-grade cytokine release syndrome or ICANS, no prolonged bone marrow toxic effects, low levels of infection, and only a moderate reduction in total immunoglobulin levels. Additionally, all 15 patients were able to terminate immunosuppressive therapy, without relapse or disease progression. While the findings are promising, the authors acknowledge the need for larger, controlled clinical studies.